Type I leucocyte adhesion deficiency (LAD I). Report of a case

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Report of a case" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "254" "paginaFinal" => "258" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M.B. García, O. Domínguez, M. Juan, J.I. Aróstegui, I. Badell, E. Chapman, M.A. Martín-Mateos" "autores" => array:7 [ 0 => array:4 [ "nombre" => "M.B." "apellidos" => "García" "email" => array:1 [ 0 => "marabagarcia@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "O." "apellidos" => "Domínguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Juan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J.I." "apellidos" => "Aróstegui" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "I." "apellidos" => "Badell" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "E." "apellidos" => "Chapman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "M.A." "apellidos" => "Martín-Mateos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Section of Immunology and Pediatric Allergy, Sant Joan de Deu Hospital, University of Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Immunology, Clinic Hospital, University of Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Transplant Unit, Sant Pau Hospital, Barcelona Autonomous University, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1313 "Ancho" => 3283 "Tamanyo" => 290518 ] ] "descripcion" => array:1 [ "en" => "Flow cytometry, CD18." ] ] ] "textoCompleto" => "Leucocyte adhesion deficiencies (LADs) are a group of primary immunodeficiencies in which the leucocytes are unable to migrate from the circulation towards the areas of inflammation. Three types of LAD have been described to date<a class="elsevierStyleCrossRefs" href="#bib0005">1–3</a>:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Type I leucocyte adhesion deficiency (LAD I), characterised by mutations in the common chain (CD18) of the β2 integrins family. These patients suffer serious recurrent infections of the skin and mucosal membranes. In the more serious presentations the patients die early if haematopoietic precursor cell transplantation is not carried out.<a class="elsevierStyleCrossRefs" href="#bib0005">1–3</a></li><li class="elsevierStyleListItem" id="lsti0010">2.Type II leucocyte adhesion deficiency (LAD II), characterised by the absence of the fucosylated ligand in neutrophils needed for binding to selectins E and P in the activated endothelium. Clinically, these patients suffer less serious infections but present retarded psychomotor and weight and body height development.<a class="elsevierStyleCrossRefs" href="#bib0005">1–3</a></li><li class="elsevierStyleListItem" id="lsti0015">3.Type III leucocyte adhesion deficiency (LAD III), characterised by a defect in the activation of integrins β1, β2 and β3. These patients suffer serious infections and bleeding disorders.<a class="elsevierStyleCrossRefs" href="#bib0005">1–3</a></li></ul>We present a case of type I leucocyte adhesion deficiency (LAD I).The patient in this case was a 3-month-old boy, the first offspring of consanguineous parents (first cousins). There had been no previous miscarriages. The female first cousin of the parents had died 15 days after birth due to non-established causes. Pregnancy and delivery were without complications. The patient was born to term with a body weight concordant with the gestational age. Weight and height progression was normal. Seven days after birth the patient was admitted due to omphalitis, with culture positive for penicillin-sensitive Streptococcus mitis and multisensitive Escherichia coli. Blood culture proved negative, and the complete blood count showed 42,500leucocytes/mm3 with a normal formula. At 2 months of age the patient was again admitted due to urinary infection caused by multiresistant E. coli and staphylococcal impetigo. At 3 months of age he was admitted due to left-side acute otitis media. The complete blood count showed 33,600leucocytes/mm3 (56.9% neutrophils and 31.6% lymphocytes). Two weeks later the patient developed an ulceration in the lumbar and intergluteal zone that again required admission to hospital. The patient was found to be in good general condition, with a weight of 6kg and no fever. A rounded, ulcerated non-suppurative lesion with an erythematous margin was confirmed in the lumbar and intergluteal zone (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Blood tests: leucocyte count 26,500cells/mm3 (31% neutrophils and 53.9% lymphocytes), C-reactive protein 6mg/l, erythrocyte sedimentation rate 11mm/h, with negative blood and lesion sample cultures. Empirical antibiotic treatment was started with meropenem. An immune study was carried out, revealing the following lymphoid population distribution: LB 18%, LT 62%, LT4 46%, LT8 15%, absolute LT4 6578/mm3. IgM: 3038mg/l, IgG: 4627mg/l, IgA: 437mg/l, IgE: 47kU/l. Neutrophil oxidative capacity test 96%, as determined by flow cytometry with dihydrorhodamine. Leucocyte adhesion deficiency (LAD) was suspected, as a result of which flow cytometry with anti-CD11/CD18 monoclonal antibodies was carried out, revealing the absence of CD18 in leucocytes (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The blood group corresponded to A+ (discarding group hh Bombay present in type II leucocyte adhesion defect). An ITGB2 gene mutation analysis was performed, revealing the presence of genetic mutation p.Gly-169-Arg (also known as p.G169R) in exon 5 of the mentioned gene and in both alleles (homozygosis). Given the compatible clinical manifestations, the total absence of CD18 expression in peripheral blood leucocytes, and the presence of mutation p.G169R, we concluded that the patient suffered a severe type I leucocyte adhesion defect. Study of both parents was decided on in order to establish the segregation pattern of the detected mutation. Flow cytometric analysis of both parents revealed CD18 present in 98% of the leucocytes, while mutation analysis of the ITGB2 gene showed the presence in both parents of the same mutation identified in the patient, though in only one of the two alleles (heterozygosis) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The patient posteriorly required further admissions due to impetigo on two occasions, urinary infection caused by E. coli, and periodontitis – with persistently elevated leucocyte and neutrophil counts.The definitive diagnosis was type I leucocyte adhesion deficiency (LAD I), with severe phenotype: mutation p.G169R in exon 5 of the ITGB2 gene in homozygosis. Healthy parents carrying the mutation in heterozygosis.Early antibiotic therapy was started on occasion of all recurrences, followed by a good clinical course. Regarding aetiological treatment, HLA typing of the patient was started, together with the search for a haematopoietic precursor cell donor. At the age of 19 months peripheral blood allogenic haematopoietic precursor cell transplantation from an unrelated donor was carried out (Id 9/10 molecular). Transplantation was started with non-myeloablative conditioning treatment administering CAMPATH-1 at a dose of 0.2mg/kg/day i.v. for 5 days, fludarabine 30mg/m2/day i.v. for 5 days, melphalan 140mg/m2 i.v. and allopurinol p.o. 300mg/m2/day for 7 days. Prophylaxis against graft-versus-host disease was provided with cyclosporine 1.5mg/kg/12h i.v. from day −1 to day +30, plus mycophenolate 7.5mg/kg/12h from day −1 to day +30. The patient moreover also received prophylactic antibiotic, antiviral and antifungal therapy. Haematopoietic precursor cell infusion was carried out without complications, and followed by haematological recovery. The patient posteriorly developed infectious complications caused by CMV (with PCR positive for CMV), for which gancyclovir was prescribed, as well as adenovirus infection (coproculture positive for adenovirus) for which cidofovir was prescribed, and infection due to Aspergillus (galactomannan antigen positive in blood), for which voriconazole was administered. Haematological toxicity was moreover observed, requiring red cell and platelet transfusions. The patient developed acute cutaneous, gastrointestinal and hepatic graft-versus-host disease, receiving treatment with prednisone, topical triamcinolone, Leukotac and tacrolimus. Death occurred two and a half months after transplantation as a result of these complications.A non-specific (innate) immune response is triggered as a result of infection. The neutrophils and monocytes are attracted from the peripheral circulation towards the site of infection, binding to adhesion molecules located on the endothelial cells, and responding to chemotactic factors produced as a consequence of the infection.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> This phenomenon takes place in four phases:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">(1)Extension of the leucocytes over the endothelium, due to the action of the selectins which rapidly increase their expression on the surface of the endothelial cells of the postcapillary veins at the site of infection. The two types of selectins expressed by the endothelial cells are selectin P and E. A third type called selectin L is expressed by lymphocytes and other leucocytes. The selectins allow the neutrophils to adhere to the endothelial cells, which in turn have been activated through the action of cytokines (TNF, IL1 and IFNγ) present in the inflammatory focus.</li><li class="elsevierStyleListItem" id="lsti0025">(2)Increased integrin affinity as a result of chemokine activity. The chemokines stimulate cell chemotaxis. The integrins are heterodymer compounds of covalently bonded α and β protein chains.<a class="elsevierStyleCrossRef" href="#bib0020">4</a></li><li class="elsevierStyleListItem" id="lsti0030">(3)Leucocyte adhesion to the endothelium. The cytokines also favor endothelial ligand expression, particularly vascular cell adhesion molecule-1 (VCAM-1, a ligand for integrin VLA-4), and intercellular adhesion molecule-1 (ICAM-1, a ligand for integrins LFA-1 and Mac-1). This leads to free binding of the leucocytes to the endothelium.<a class="elsevierStyleCrossRef" href="#bib0020">4</a></li><li class="elsevierStyleListItem" id="lsti0035">(4)Transmigration of the leucocytes through the endothelium: The chemokines act upon the adhered leucocytes and stimulate cell migration through the inter-endothelial spaces towards the site of infection.<a class="elsevierStyleCrossRef" href="#bib0020">4</a></li></ul>An alteration in any of the steps of the above process will result in defective leucocyte migration.The present clinical case corresponds to a type I leucocyte adhesion defect due to mutation p.G169R in exon 5 of the ITGB2 gene in homozygosis, exhibiting an autosomal recessive hereditary trait.LAD I is an autosomal recessive disease resulting from a quantitative or qualitative defect in the common chain (CD18) of the β2 integrins family. Over 300 cases have been reported to date.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The leucocytes of patients with LAD I are deficient in terms of the expression of the three integrins that contain CD18:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040">•Lymphocyte function antigen-1 (LFA-1, CD11a/CD18).</li><li class="elsevierStyleListItem" id="lsti0045">•Mac-1 (CD11b/CD18).</li><li class="elsevierStyleListItem" id="lsti0050">•Gp 150/95 (CD11c/CD18).</li></ul>The primary defect in this disease is related to the β2 subunit, the biosynthesis of which is necessary for surface expression of the α subunits.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The patient showed a total absence of CD18 expression in peripheral blood leucocytes, thus compromising the expression of these three integrins belonging to the β2 integrins family.In vitro studies have shown important defects in chemotaxis, adhesion and migration through the endothelial cell layer. This genetic disorder is due to mutations in the gene of the β2 integrin (ITGB2) encoding for the CD18 subunit, located at an extremity of the long arm of chromosome 21q22.23. The molecular bases underlying the CD18 deficiencies are variable. There have been descriptions of mutations that lead to the expression of quantitatively normal CD18 but with functional defects – although few such cases have been documented. Point mutations have been described that lead to defective protein synthesis with the substitution of a single amino acid. Other mutations lead to splicing defects, resulting in the production of unstable proteins – many of which are located at the binding site of the β2 integrins to their ICAM 1 or 2 ligands. In turn, other genetic defects result in a reduction in CD18 mRNA expression. Other cases are characterised by the expression of mRNA or proteic precursors of aberrant size, leading to large or small CD18 subunits. An important percentage of the CD18 mutations identified in LAD I are located in the extracellular domain of the CD18 subunit, in exon 9 – this being a highly preserved region. Although LAD I can be caused by a range of mutations, all result in the production of a non-functional β2 subunit. In most cases small point mutations, minor insertions or deletions are reported in the ITGB2 gene.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>Our patient presented the mutation p.Gly-169-Arg (glycine substitution by arginine in position 169) in exon 5 of the ITGB2 gene located on the long arm of chromosome 21, previously described in the literature as a mutation responsible for severe forms of type I leucocyte adhesion defect.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a>LAD I is clinically characterised by delayed shedding of the umbilical stump, recurrent bacterial infections mainly of the skin and mucosal membranes, leucocytosis, periodontitis, the absence of pus and poor wound healing.<a class="elsevierStyleCrossRefs" href="#bib0005">1,7–9</a>The severity of the infectious complications in patients with LAD I appears to be directly related to the degree of CD18 deficiency. Two phenotypes have been described that make it possible to classify the condition as corresponding to either severe or moderate deficiency disease<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055">•Severe: less than 2% of the normal expression of CD18. These patients suffer earlier, frequent and serious infections, and most die in childhood if appropriate treatment is not provided.</li><li class="elsevierStyleListItem" id="lsti0060">•Mild to moderate: CD18 expression ranges from 2 to 30% of normal. These patients suffer few serious infections, and most survive into adult life.</li></ul>Our patient presented all the clinical manifestations corresponding to the severe form of the disease.Patients of this type have difficulties defending themselves against bacteria and fungi, although they do not show an increased susceptibility to viral infections.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The infections affect the skin, respiratory tract, intestine and perirectal area usually from the time of birth. The lesions can become necrotic, ulcerating and often quickly progress towards systemic infection. A classical infectious presentation of the disorder is omphalitis, with delayed shedding of the umbilical stump (>30 days). Severe gingivitis and periodontitis are the most frequent infections among those patients who survive beyond childhood. The most commonly implicated microorganisms are Staphylococcus aureus and enteric gramnegative bacilli.<a class="elsevierStyleCrossRefs" href="#bib0005">1–3</a>Our patient suffered several infectious episodes caused by S. aureus and E. coli, and on one occasion S. mitis was isolated.The absence of pus at the sites of infection is characteristic of the disease.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Such patients have a severely limited extravascular leucocyte mobilisation capacity, as a result of which these cells are unable to reach the sites of inflammation. Biopsies of the infection sites reveal inflammation without neutrophils. In turn, there is a diminished presence of lymphocytes in the lymphoid tissue, since LFA-1 plays an important role in the function of these cells. Late shedding of the umbilical stump is one of the expressions of the poor wound healing that characterises these individuals, and is accompanied by a dystrophic appearance of the resulting scar tissue. Laboratory tests can show moderate neutrophilia in the absence of infection. During the infectious process, marked leucocytosis with neutrophilia (5–20 times greater than normal, reaching counts of up to 100,000cells/mm3) is observed, due to the incapacity to mobilise the cells towards extravascular inflammatory sites.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> This was characteristically seen in our patient.The diagnosis of the disease should be suspected in all infants with recurrent soft tissue infections and important leucocytosis. The diagnostic criteria were established in 1999<a class="elsevierStyleCrossRef" href="#bib0050">10</a>:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0065">1.Definitive diagnosis: patients with diminished CD18 expression in neutrophils (<5% of normal), and at least one of the following:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0070">-Mutation of the β2 integrin gene.</li><li class="elsevierStyleListItem" id="lsti0075">-Absence of mRNA encoding for β2 integrin in leucocytes.</li></ul></li><li class="elsevierStyleListItem" id="lsti0080">2.Probable diagnosis: patients with diminished CD18 expression in neutrophils (<5% of normal), and all of the following:<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0085">-Recurrent bacterial or fungal infections.</li><li class="elsevierStyleListItem" id="lsti0090">-Leucocytosis >25,000cells/mm3.</li><li class="elsevierStyleListItem" id="lsti0095">-Delayed shedding of the umbilical stump and/or wound healing defects.</li></ul></li><li class="elsevierStyleListItem" id="lsti0100">3.Possible diagnosis: patients with important leucocytosis >25,000cells/mm3 and one of the following:<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0105">-Recurrent bacterial infections.</li><li class="elsevierStyleListItem" id="lsti0110">-Deep-seated and severe infection.</li><li class="elsevierStyleListItem" id="lsti0115">-Absence of pus at the sites of infection.</li></ul></li></ul>Confirmation of the diagnosis requires demonstration of the absence of CD18 and the associated alpha subunit CD11a, CD11b and CD11c on the surface of the leucocytes, based on flow cytometry using monoclonal antibodies CD11 and CD18.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Sequence analysis is advised in all cases in order to define the molecular defect of the β2 subunit. Leucocytes express CD18 at surface level from week 20 of intrauterine development; as a result, cordocentesis performed after this time can contribute to establish a prenatal diagnosis.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In those families in which a molecular defect has been identified, an early prenatal diagnosis can be established via chorionic biopsy and mutation analysis. Recently, a pre-implantation diagnosis has been established.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>In most cases the clinical manifestations and laboratory test findings are suggestive of the disease and the diagnosis is clear. However, a differential diagnosis is required with conditions also characterised by important leucocytosis, such as infections, leukaemoid reactions, leucaemia and other lymphoproliferative processes.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The treatment of the disease depends on the severity of the clinical picture. In the case of the mild to moderate phenotype, the infections respond to conservative management and the early and appropriate use of antibiotics during the acute episodes. Correct oral hygiene is important for the control of periodontitis and for preventing infections. These patients can receive all vaccines, including those involving live viruses. Prophylactic antibiotic treatment can reduce the risk of infection, and adequate management of the infectious processes can allow such patients to survive into adulthood.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>In the case of patients with the severe disease phenotype, the only corrective treatment available to date is the transplantation of haematopoietic precursor cells.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2,12,13</a> The absence of LFA-1 in these patients can constitute an advantage for transplantation, since graft rejection appears to depend in part on the CD18 complex. The largest series published to date describes 36 children in 14 centres subjected to transplantation between 1993 and 2007, and followed-up on for 5 years after transplantation. The reported survival rate was 75%. Low-intensity conditioning regimens were found to be safe.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Transplant success depends on early diagnosis and treatment, the conditioning regimen used before transplantation, and the degree of donor compatibility. Gene therapy has been evaluated in the context of preclinical and in vivo trials, inserting a normal ITGB2 gene in haematopoietic stem cells, with promising results.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> However, further studies are needed to support the results obtained. These patients die in childhood if transplantation is not carried out as soon as possible. If transplantation is performed before serious infections develop, the resulting prognosis is very good.To summarise, our patient presented the typical clinical characteristics of type I leucocyte adhesion deficiency (LAD I), i.e., omphalitis, late shedding of the umbilical stump, recurrent infections of the skin and mucosal membranes without pus formation, persistently elevated leucocyte counts and flow cytometric findings indicative of the severe phenotype of the disease. The diagnosis in turn was confirmed by the genetic study. Although LAD I is a rare form of congenital immune deficiency, it must be taken into account in patients who present this clinical picture." "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 2500 "Tamanyo" => 166955 ] ] "descripcion" => array:1 [ "en" => "Clinical manifestations of LAD I." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1313 "Ancho" => 3283 "Tamanyo" => 290518 ] ] "descripcion" => array:1 [ "en" => "Flow cytometry, CD18." ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Clinical manifestations</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Clinical manifestation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Microorganism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Omphalitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Streptococcus mitisEscherichia coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ampicillin–gentamycin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 month \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative cultures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amoxicillin–clavulanate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urinary infectionImpetigo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Escherichia coliStaphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cefuroxime \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute otitis media \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amoxicillin–clavulanate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genital ulcer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative cultures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meropenem \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cheek impetigo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amoxicillin–clavulanate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urinary infectionAcute otitis media \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Escherichia coli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ceftriaxone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute otitis media \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amoxicillin–clavulanate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Impetigo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative cultures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amoxicillin–clavulanate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Periodontitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative cultures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vancomycin–meropenem \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165533.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical manifestations of LAD I." ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Non-specific immunity study, adhesion molecules</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD18 in leucocytes (flow cytometry) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A+ \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165535.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="8" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Genetic study</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Exons studied \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Results \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Nucleotide substitution \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Amino acid change \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Status \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ITGB2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type I LAD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1→15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 mutations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">c. 505 G→A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p.Gly-169-Arg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Homozygosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr 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M.B. Garcíaa,

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marabagarcia@yahoo.com

Corresponding author.

, O. Domíngueza, M. Juanb, J.I. Arósteguib, I. Badellc, E. Chapmana, M.A. Martín-Mateosa

a Section of Immunology and Pediatric Allergy, Sant Joan de Deu Hospital, University of Barcelona, Spain

b Department of Immunology, Clinic Hospital, University of Barcelona, Spain

c Transplant Unit, Sant Pau Hospital, Barcelona Autonomous University, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Leucocyte adhesion deficiencies &#40;LADs&#41; are a group of primary immunodeficiencies in which the leucocytes are unable to migrate from the circulation towards the areas of inflammation&#46; Three types of LAD have been described to date<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a>&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0010" class="elsevierStylePara elsevierViewall">Type I leucocyte adhesion deficiency &#40;LAD I&#41;&#44; characterised by mutations in the common chain &#40;CD18&#41; of the &#946;2 integrins family&#46; These patients suffer serious recurrent infections of the skin and mucosal membranes&#46; In the more serious presentations the patients die early if haematopoietic precursor cell transplantation is not carried out&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Type II leucocyte adhesion deficiency &#40;LAD II&#41;&#44; characterised by the absence of the fucosylated ligand in neutrophils needed for binding to selectins E and P in the activated endothelium&#46; Clinically&#44; these patients suffer less serious infections but present retarded psychomotor and weight and body height development&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Type III leucocyte adhesion deficiency &#40;LAD III&#41;&#44; characterised by a defect in the activation of integrins &#946;1&#44; &#946;2 and &#946;3&#46; These patients suffer serious infections and bleeding disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p></li></ul></p><p id="par0025" class="elsevierStylePara elsevierViewall">We present a case of type I leucocyte adhesion deficiency &#40;LAD I&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient in this case was a 3-month-old boy&#44; the first offspring of consanguineous parents &#40;first cousins&#41;&#46; There had been no previous miscarriages&#46; The female first cousin of the parents had died 15 days after birth due to non-established causes&#46; Pregnancy and delivery were without complications&#46; The patient was born to term with a body weight concordant with the gestational age&#46; Weight and height progression was normal&#46; Seven days after birth the patient was admitted due to omphalitis&#44; with culture positive for penicillin-sensitive <span class="elsevierStyleItalic">Streptococcus mitis</span> and multisensitive <span class="elsevierStyleItalic">Escherichia coli</span>&#46; Blood culture proved negative&#44; and the complete blood count showed 42&#44;500<span class="elsevierStyleHsp" style=""></span>leucocytes&#47;mm<span class="elsevierStyleSup">3</span> with a normal formula&#46; At 2 months of age the patient was again admitted due to urinary infection caused by multiresistant <span class="elsevierStyleItalic">E&#46; coli</span> and staphylococcal impetigo&#46; At 3 months of age he was admitted due to left-side acute otitis media&#46; The complete blood count showed 33&#44;600<span class="elsevierStyleHsp" style=""></span>leucocytes&#47;mm<span class="elsevierStyleSup">3</span> &#40;56&#46;9&#37; neutrophils and 31&#46;6&#37; lymphocytes&#41;&#46; Two weeks later the patient developed an ulceration in the lumbar and intergluteal zone that again required admission to hospital&#46; The patient was found to be in good general condition&#44; with a weight of 6<span class="elsevierStyleHsp" style=""></span>kg and no fever&#46; A rounded&#44; ulcerated non-suppurative lesion with an erythematous margin was confirmed in the lumbar and intergluteal zone &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Blood tests&#58; leucocyte count 26&#44;500<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> &#40;31&#37; neutrophils and 53&#46;9&#37; lymphocytes&#41;&#44; C-reactive protein 6<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; erythrocyte sedimentation rate 11<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#44; with negative blood and lesion sample cultures&#46; Empirical antibiotic treatment was started with meropenem&#46; An immune study was carried out&#44; revealing the following lymphoid population distribution&#58; LB 18&#37;&#44; LT 62&#37;&#44; LT4 46&#37;&#44; LT8 15&#37;&#44; absolute LT4 6578&#47;mm<span class="elsevierStyleSup">3</span>&#46; IgM&#58; 3038<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; IgG&#58; 4627<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; IgA&#58; 437<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; IgE&#58; 47<span class="elsevierStyleHsp" style=""></span>kU&#47;l&#46; Neutrophil oxidative capacity test 96&#37;&#44; as determined by flow cytometry with dihydrorhodamine&#46; Leucocyte adhesion deficiency &#40;LAD&#41; was suspected&#44; as a result of which flow cytometry with anti-CD11&#47;CD18 monoclonal antibodies was carried out&#44; revealing the absence of CD18 in leucocytes &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The blood group corresponded to A&#43; &#40;discarding group hh Bombay present in type II leucocyte adhesion defect&#41;&#46; An ITGB2 gene mutation analysis was performed&#44; revealing the presence of genetic mutation p&#46;Gly-169-Arg &#40;also known as p&#46;G169R&#41; in exon 5 of the mentioned gene and in both alleles &#40;homozygosis&#41;&#46; Given the compatible clinical manifestations&#44; the total absence of CD18 expression in peripheral blood leucocytes&#44; and the presence of mutation p&#46;G169R&#44; we concluded that the patient suffered a severe type I leucocyte adhesion defect&#46; Study of both parents was decided on in order to establish the segregation pattern of the detected mutation&#46; Flow cytometric analysis of both parents revealed CD18 present in 98&#37; of the leucocytes&#44; while mutation analysis of the ITGB2 gene showed the presence in both parents of the same mutation identified in the patient&#44; though in only one of the two alleles &#40;heterozygosis&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient posteriorly required further admissions due to impetigo on two occasions&#44; urinary infection caused by <span class="elsevierStyleItalic">E&#46; coli</span>&#44; and periodontitis &#8211; with persistently elevated leucocyte and neutrophil counts&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The definitive diagnosis was type I leucocyte adhesion deficiency &#40;LAD I&#41;&#44; with severe phenotype&#58; mutation p&#46;G169R in exon 5 of the ITGB2 gene in homozygosis&#46; Healthy parents carrying the mutation in heterozygosis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Early antibiotic therapy was started on occasion of all recurrences&#44; followed by a good clinical course&#46; Regarding aetiological treatment&#44; HLA typing of the patient was started&#44; together with the search for a haematopoietic precursor cell donor&#46; At the age of 19 months peripheral blood allogenic haematopoietic precursor cell transplantation from an unrelated donor was carried out &#40;Id 9&#47;10 molecular&#41;&#46; Transplantation was started with non-myeloablative conditioning treatment administering CAMPATH-1 at a dose of 0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day i&#46;v&#46; for 5 days&#44; fludarabine 30<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#47;day i&#46;v&#46; for 5 days&#44; melphalan 140<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> i&#46;v&#46; and allopurinol p&#46;o&#46; 300<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span>&#47;day for 7 days&#46; Prophylaxis against graft-versus-host disease was provided with cyclosporine 1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;12<span class="elsevierStyleHsp" style=""></span>h i&#46;v&#46; from day &#8722;1 to day &#43;30&#44; plus mycophenolate 7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;12<span class="elsevierStyleHsp" style=""></span>h from day &#8722;1 to day &#43;30&#46; The patient moreover also received prophylactic antibiotic&#44; antiviral and antifungal therapy&#46; Haematopoietic precursor cell infusion was carried out without complications&#44; and followed by haematological recovery&#46; The patient posteriorly developed infectious complications caused by CMV &#40;with PCR positive for CMV&#41;&#44; for which gancyclovir was prescribed&#44; as well as adenovirus infection &#40;coproculture positive for adenovirus&#41; for which cidofovir was prescribed&#44; and infection due to <span class="elsevierStyleItalic">Aspergillus</span> &#40;galactomannan antigen positive in blood&#41;&#44; for which voriconazole was administered&#46; Haematological toxicity was moreover observed&#44; requiring red cell and platelet transfusions&#46; The patient developed acute cutaneous&#44; gastrointestinal and hepatic graft-versus-host disease&#44; receiving treatment with prednisone&#44; topical triamcinolone&#44; Leukotac and tacrolimus&#46; Death occurred two and a half months after transplantation as a result of these complications&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">A non-specific &#40;innate&#41; immune response is triggered as a result of infection&#46; The neutrophils and monocytes are attracted from the peripheral circulation towards the site of infection&#44; binding to adhesion molecules located on the endothelial cells&#44; and responding to chemotactic factors produced as a consequence of the infection&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This phenomenon takes place in four phases&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#40;1&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Extension of the leucocytes over the endothelium&#44; due to the action of the selectins which rapidly increase their expression on the surface of the endothelial cells of the postcapillary veins at the site of infection&#46; The two types of selectins expressed by the endothelial cells are selectin P and E&#46; A third type called selectin L is expressed by lymphocytes and other leucocytes&#46; The selectins allow the neutrophils to adhere to the endothelial cells&#44; which in turn have been activated through the action of cytokines &#40;TNF&#44; IL1 and IFN&#947;&#41; present in the inflammatory focus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#40;2&#41;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Increased integrin affinity as a result of chemokine activity&#46; The chemokines stimulate cell chemotaxis&#46; The integrins are heterodymer compounds of covalently bonded &#945; and &#946; protein chains&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#40;3&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Leucocyte adhesion to the endothelium&#46; The cytokines also favor endothelial ligand expression&#44; particularly vascular cell adhesion molecule-1 &#40;VCAM-1&#44; a ligand for integrin VLA-4&#41;&#44; and intercellular adhesion molecule-1 &#40;ICAM-1&#44; a ligand for integrins LFA-1 and Mac-1&#41;&#46; This leads to free binding of the leucocytes to the endothelium&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#40;4&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Transmigration of the leucocytes through the endothelium&#58; The chemokines act upon the adhered leucocytes and stimulate cell migration through the inter-endothelial spaces towards the site of infection&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">An alteration in any of the steps of the above process will result in defective leucocyte migration&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The present clinical case corresponds to a type I leucocyte adhesion defect due to mutation p&#46;G169R in exon 5 of the ITGB2 gene in homozygosis&#44; exhibiting an autosomal recessive hereditary trait&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">LAD I is an autosomal recessive disease resulting from a quantitative or qualitative defect in the common chain &#40;CD18&#41; of the &#946;2 integrins family&#46; Over 300 cases have been reported to date&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The leucocytes of patients with LAD I are deficient in terms of the expression of the three integrins that contain CD18&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Lymphocyte function antigen-1 &#40;LFA-1&#44; CD11a&#47;CD18&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Mac-1 &#40;CD11b&#47;CD18&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Gp 150&#47;95 &#40;CD11c&#47;CD18&#41;&#46;</p></li></ul></p><p id="par0105" class="elsevierStylePara elsevierViewall">The primary defect in this disease is related to the &#946;2 subunit&#44; the biosynthesis of which is necessary for surface expression of the &#945; subunits&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The patient showed a total absence of CD18 expression in peripheral blood leucocytes&#44; thus compromising the expression of these three integrins belonging to the &#946;2 integrins family&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In vitro studies have shown important defects in chemotaxis&#44; adhesion and migration through the endothelial cell layer&#46; This genetic disorder is due to mutations in the gene of the &#946;2 integrin &#40;ITGB2&#41; encoding for the CD18 subunit&#44; located at an extremity of the long arm of chromosome 21q22&#46;23&#46; The molecular bases underlying the CD18 deficiencies are variable&#46; There have been descriptions of mutations that lead to the expression of quantitatively normal CD18 but with functional defects &#8211; although few such cases have been documented&#46; Point mutations have been described that lead to defective protein synthesis with the substitution of a single amino acid&#46; Other mutations lead to splicing defects&#44; resulting in the production of unstable proteins &#8211; many of which are located at the binding site of the &#946;2 integrins to their ICAM 1 or 2 ligands&#46; In turn&#44; other genetic defects result in a reduction in CD18 mRNA expression&#46; Other cases are characterised by the expression of mRNA or proteic precursors of aberrant size&#44; leading to large or small CD18 subunits&#46; An important percentage of the CD18 mutations identified in LAD I are located in the extracellular domain of the CD18 subunit&#44; in exon 9 &#8211; this being a highly preserved region&#46; Although LAD I can be caused by a range of mutations&#44; all result in the production of a non-functional &#946;2 subunit&#46; In most cases small point mutations&#44; minor insertions or deletions are reported in the ITGB2 gene&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Our patient presented the mutation p&#46;Gly-169-Arg &#40;glycine substitution by arginine in position 169&#41; in exon 5 of the ITGB2 gene located on the long arm of chromosome 21&#44; previously described in the literature as a mutation responsible for severe forms of type I leucocyte adhesion defect&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">LAD I is clinically characterised by delayed shedding of the umbilical stump&#44; recurrent bacterial infections mainly of the skin and mucosal membranes&#44; leucocytosis&#44; periodontitis&#44; the absence of pus and poor wound healing&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7&#8211;9</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The severity of the infectious complications in patients with LAD I appears to be directly related to the degree of CD18 deficiency&#46; Two phenotypes have been described that make it possible to classify the condition as corresponding to either severe or moderate deficiency disease<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a>&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Severe&#58; less than 2&#37; of the normal expression of CD18&#46; These patients suffer earlier&#44; frequent and serious infections&#44; and most die in childhood if appropriate treatment is not provided&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Mild to moderate&#58; CD18 expression ranges from 2 to 30&#37; of normal&#46; These patients suffer few serious infections&#44; and most survive into adult life&#46;</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">Our patient presented all the clinical manifestations corresponding to the severe form of the disease&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Patients of this type have difficulties defending themselves against bacteria and fungi&#44; although they do not show an increased susceptibility to viral infections&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The infections affect the skin&#44; respiratory tract&#44; intestine and perirectal area usually from the time of birth&#46; The lesions can become necrotic&#44; ulcerating and often quickly progress towards systemic infection&#46; A classical infectious presentation of the disorder is omphalitis&#44; with delayed shedding of the umbilical stump &#40;&#62;30 days&#41;&#46; Severe gingivitis and periodontitis are the most frequent infections among those patients who survive beyond childhood&#46; The most commonly implicated microorganisms are <span class="elsevierStyleItalic">Staphylococcus aureus</span> and enteric gramnegative bacilli&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Our patient suffered several infectious episodes caused by <span class="elsevierStyleItalic">S&#46; aureus</span> and <span class="elsevierStyleItalic">E&#46; coli</span>&#44; and on one occasion <span class="elsevierStyleItalic">S&#46; mitis</span> was isolated&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The absence of pus at the sites of infection is characteristic of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Such patients have a severely limited extravascular leucocyte mobilisation capacity&#44; as a result of which these cells are unable to reach the sites of inflammation&#46; Biopsies of the infection sites reveal inflammation without neutrophils&#46; In turn&#44; there is a diminished presence of lymphocytes in the lymphoid tissue&#44; since LFA-1 plays an important role in the function of these cells&#46; Late shedding of the umbilical stump is one of the expressions of the poor wound healing that characterises these individuals&#44; and is accompanied by a dystrophic appearance of the resulting scar tissue&#46; Laboratory tests can show moderate neutrophilia in the absence of infection&#46; During the infectious process&#44; marked leucocytosis with neutrophilia &#40;5&#8211;20 times greater than normal&#44; reaching counts of up to 100&#44;000<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#41; is observed&#44; due to the incapacity to mobilise the cells towards extravascular inflammatory sites&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This was characteristically seen in our patient&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The diagnosis of the disease should be suspected in all infants with recurrent soft tissue infections and important leucocytosis&#46; The diagnostic criteria were established in 1999<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">1&#46;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Definitive diagnosis&#58; patients with diminished CD18 expression in neutrophils &#40;&#60;5&#37; of normal&#41;&#44; and at least one of the following&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0175" class="elsevierStylePara elsevierViewall">Mutation of the &#946;2 integrin gene&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">Absence of mRNA encoding for &#946;2 integrin in leucocytes&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">2&#46;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Probable diagnosis&#58; patients with diminished CD18 expression in neutrophils &#40;&#60;5&#37; of normal&#41;&#44; and all of the following&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0190" class="elsevierStylePara elsevierViewall">Recurrent bacterial or fungal infections&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">Leucocytosis &#62;25&#44;000<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Delayed shedding of the umbilical stump and&#47;or wound healing defects&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">3&#46;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Possible diagnosis&#58; patients with important leucocytosis &#62;25&#44;000<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span> and one of the following&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">Recurrent bacterial infections&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0215" class="elsevierStylePara elsevierViewall">Deep-seated and severe infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">Absence of pus at the sites of infection&#46;</p></li></ul></p></li></ul></p><p id="par0225" class="elsevierStylePara elsevierViewall">Confirmation of the diagnosis requires demonstration of the absence of CD18 and the associated alpha subunit CD11a&#44; CD11b and CD11c on the surface of the leucocytes&#44; based on flow cytometry using monoclonal antibodies CD11 and CD18&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Sequence analysis is advised in all cases in order to define the molecular defect of the &#946;2 subunit&#46; Leucocytes express CD18 at surface level from week 20 of intrauterine development&#59; as a result&#44; cordocentesis performed after this time can contribute to establish a prenatal diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In those families in which a molecular defect has been identified&#44; an early prenatal diagnosis can be established via chorionic biopsy and mutation analysis&#46; Recently&#44; a pre-implantation diagnosis has been established&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In most cases the clinical manifestations and laboratory test findings are suggestive of the disease and the diagnosis is clear&#46; However&#44; a differential diagnosis is required with conditions also characterised by important leucocytosis&#44; such as infections&#44; leukaemoid reactions&#44; leucaemia and other lymphoproliferative processes&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">The treatment of the disease depends on the severity of the clinical picture&#46; In the case of the mild to moderate phenotype&#44; the infections respond to conservative management and the early and appropriate use of antibiotics during the acute episodes&#46; Correct oral hygiene is important for the control of periodontitis and for preventing infections&#46; These patients can receive all vaccines&#44; including those involving live viruses&#46; Prophylactic antibiotic treatment can reduce the risk of infection&#44; and adequate management of the infectious processes can allow such patients to survive into adulthood&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">In the case of patients with the severe disease phenotype&#44; the only corrective treatment available to date is the transplantation of haematopoietic precursor cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2&#44;12&#44;13</span></a> The absence of LFA-1 in these patients can constitute an advantage for transplantation&#44; since graft rejection appears to depend in part on the CD18 complex&#46; The largest series published to date describes 36 children in 14 centres subjected to transplantation between 1993 and 2007&#44; and followed-up on for 5 years after transplantation&#46; The reported survival rate was 75&#37;&#46; Low-intensity conditioning regimens were found to be safe&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Transplant success depends on early diagnosis and treatment&#44; the conditioning regimen used before transplantation&#44; and the degree of donor compatibility&#46; Gene therapy has been evaluated in the context of preclinical and in vivo trials&#44; inserting a normal ITGB2 gene in haematopoietic stem cells&#44; with promising results&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> However&#44; further studies are needed to support the results obtained&#46; These patients die in childhood if transplantation is not carried out as soon as possible&#46; If transplantation is performed before serious infections develop&#44; the resulting prognosis is very good&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">To summarise&#44; our patient presented the typical clinical characteristics of type I leucocyte adhesion deficiency &#40;LAD I&#41;&#44; i&#46;e&#46;&#44; omphalitis&#44; late shedding of the umbilical stump&#44; recurrent infections of the skin and mucosal membranes without pus formation&#44; persistently elevated leucocyte counts and flow cytometric findings indicative of the severe phenotype of the disease&#46; The diagnosis in turn was confirmed by the genetic study&#46; Although LAD I is a rare form of congenital immune deficiency&#44; it must be taken into account in patients who present this clinical picture&#46;</p></span>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Clinical manifestations</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Clinical manifestation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Microorganism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omphalitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Streptococcus mitis</span><span class="elsevierStyleItalic">Escherichia coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ampicillin&#8211;gentamycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amoxicillin&#8211;clavulanate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urinary infectionImpetigo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Escherichia coli</span><span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cefuroxime&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute otitis media&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amoxicillin&#8211;clavulanate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genital ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Meropenem&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cheek impetigo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amoxicillin&#8211;clavulanate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urinary infectionAcute otitis media&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Escherichia coli</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ceftriaxone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute otitis media&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amoxicillin&#8211;clavulanate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Impetigo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Amoxicillin&#8211;clavulanate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Periodontitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative cultures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vancomycin&#8211;meropenem&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab165533.png"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Clinical manifestations of LAD I&#46;</p>"
        ]
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Non-specific immunity study&#44; adhesion molecules</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD18 in leucocytes &#40;flow cytometry&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blood group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&#43;&nbsp;\t\t\t\t\t\t\n
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                  """
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="8" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Genetic study</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Gene&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Exons studied&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Nucleotide substitution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Amino acid change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITGB2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Type I LAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 mutations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46; 505 G<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p&#46;Gly-169-Arg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Homozygosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Father&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITGB2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Type I LAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exon 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;505 G<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p&#46;Gly-169-Arg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heterozygosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mother&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ITGB2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Type I LAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exon 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">c&#46;505 G<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p&#46;Gly-169-Arg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Heterozygosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Non-specific &#40;innate&#41; immunity study in LAD I&#46;</p>"
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:14 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cell adhesion and leukocyte adhesion defects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Etzioni"
                            1 => "J&#46;M&#46; Harlan"
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                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:5 [
                        "titulo" => "Primary immunodeficiency diseases"
                        "paginaInicial" => "550"
                        "paginaFinal" => "561"
                        "edicion" => "2nd edition"
                        "serieFecha" => "2007"
                      ]
                    ]
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              "etiqueta" => "2"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defects in the leukocyte adhesion cascade"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Etzioni"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12016-009-8132-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rev Allergy Immunol"
                        "fecha" => "2010"
                        "volumen" => "38"
                        "paginaInicial" => "54"
                        "paginaFinal" => "60"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19437145"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leukocyte adhesion deficiencies&#58; molecular basis&#44; clinical findings and therapeutic options"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Etzioni"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Exp Med Biol"
                        "fecha" => "2007"
                        "volumen" => "601"
                        "paginaInicial" => "51"
                        "paginaFinal" => "60"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17712991"
                            "web" => "Medline"
                          ]
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                      ]
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                ]
              ]
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            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inmunologia celular y molecular"
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2011.05.013

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Year/Month	Html	Pdf	Total

2024 November	24	7	31
2024 October	106	43	149
2024 September	128	42	170
2024 August	88	35	123
2024 July	112	29	141
2024 June	112	30	142
2024 May	124	42	166
2024 April	79	26	105
2024 March	111	24	135
2024 February	124	38	162
2024 January	160	38	198
2023 December	149	49	198
2023 November	219	57	276
2023 October	184	69	253
2023 September	126	24	150
2023 August	108	24	132
2023 July	107	37	144
2023 June	138	34	172
2023 May	164	66	230
2023 April	230	80	310
2023 March	205	51	256
2023 February	92	38	130
2023 January	100	45	145
2022 December	101	30	131
2022 November	81	34	115
2022 October	105	42	147
2022 September	106	40	146
2022 August	90	37	127
2022 July	80	34	114
2022 June	90	29	119
2022 May	137	39	176
2022 April	290	51	341
2022 March	223	51	274
2022 February	279	51	330
2022 January	152	62	214
2021 December	98	56	154
2021 November	127	65	192
2021 October	90	64	154
2021 September	66	56	122
2021 August	67	40	107
2021 July	42	21	63
2021 June	34	21	55
2021 May	32	18	50
2021 April	63	39	102
2021 March	15	53	68
2021 February	10	22	32
2021 January	20	18	38
2020 December	0	4	4
2020 November	0	7	7
2020 October	0	4	4
2020 August	0	1	1
2020 July	0	2	2
2020 June	0	2	2
2020 May	0	1	1
2020 April	0	2	2
2020 March	0	1	1
2020 February	0	3	3
2020 January	0	3	3
2019 December	0	1	1
2019 November	0	2	2
2019 October	0	5	5
2019 September	0	3	3
2019 August	0	2	2
2019 July	0	8	8
2019 June	0	2	2
2019 May	0	19	19
2018 March	3	1	4
2018 February	49	1	50
2018 January	24	2	26
2017 December	36	3	39
2017 November	46	5	51
2017 October	35	8	43
2017 September	38	7	45
2017 August	59	6	65
2017 July	94	7	101
2017 June	50	12	62
2017 May	77	13	90
2017 April	67	3	70
2017 March	57	43	100
2017 February	47	3	50
2017 January	23	4	27
2016 December	25	3	28
2016 November	38	4	42
2016 October	41	3	44
2016 September	84	9	93
2016 August	103	59	162
2016 July	51	10	61
2016 June	33	7	40
2016 May	24	4	28
2016 April	39	17	56
2016 March	27	9	36
2016 February	164	42	206
2016 January	30	11	41
2015 December	22	13	35
2015 November	33	2	35
2015 October	35	8	43
2015 September	38	5	43
2015 August	50	4	54
2015 July	80	2	82
2015 June	29	4	33
2015 May	55	2	57
2015 April	69	7	76
2015 March	99	6	105
2015 February	11	0	11
2015 January	18	6	24
2014 December	28	7	35
2014 November	13	2	15
2014 October	28	9	37
2014 September	18	5	23
2014 August	25	2	27
2014 July	22	6	28
2014 June	20	2	22
2014 May	11	2	13
2014 April	2	3	5
2014 March	79	12	91
2014 February	83	13	96
2014 January	65	12	77
2013 December	47	7	54
2013 November	47	9	56
2013 October	80	8	88
2013 September	64	17	81
2013 August	148	18	166
2013 July	72	8	80
2013 June	45	5	50
2013 May	57	9	66
2013 April	42	11	53
2013 March	24	6	30
2013 February	17	7	24
2013 January	11	4	15
2012 December	12	4	16
2012 November	7	5	12
2012 October	2	2	4
2012 September	3	2	5
2012 June	372	0	372

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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