Original article
AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency
E. Farhadia,b, S. Nematic, A.A. Amirzargara,c, A. Hirbod-Mobarakeha,d, M. Nabavie, S. Soltania, S.A. Mahdavianif, S. Shahinpourg, S. Arshie, B. Nikbina,c, A. Aghamohammadig, N. Rezaeia,c,g,
Corresponding author
a Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
b Hematology Department, School of Allied Medical Science, Tehran University of Medical Sciences, Tehran, Iran
c Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
d Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
e Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran
f Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
g Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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"apellidos" => "Farhadi" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Nemati" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "A.A." "apellidos" => "Amirzargar" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Hirbod-Mobarakeh" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Nabavi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "S." "apellidos" => "Soltani" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "S.A." "apellidos" => "Mahdaviani" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 7 => array:3 [ "nombre" => "S." 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"apellidos" => "Rezaei" "email" => array:1 [ 0 => "rezaei_nima@tums.ac.ir" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hematology Department, School of Allied Medical Science, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Allergy and Immunology, Rasool-e-Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Primary antibody deficiencies (PADs) are the most common form of primary immunodeficiency diseases (PIDs), and consist of a number of diseases, ranging from severe reduction of all serum immunoglobulins and decreased number of B-cells to selective immunoglobulin deficiency.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Common variable immunodeficiency (CVID), as the most prevalent symptomatic PID, is a heterogeneous group of disorders with reduction of at least two immunoglobulin levels; some of the patients might have substantial amounts of IgM.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–5</span></a> On the other hand, selective IgA deficiency (IgAD), another heterogeneous condition, is the most common PID, resulting in reduced level of serum IgA in the presence of normal levels of other immunoglobulins.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Although the exact pathophysiology of CVID and IgAD are still unknown, it seems that they could share a common underlying genetic defect in at least one subset of patients.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> In both diseases, terminal differentiation of B cells to plasma cells of the different isotypes is impaired. Some patients with IgAD also have IgG subclass deficiency and occasionally they can progress to CVID.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Both diseases may occur in different members of the same family.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,9</span></a> Several common susceptibility haplotypes in three classes of major histocompatibility complex (MHC) have been found in CVID and IgAD.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,10</span></a> These observations suggest that genetic factors play a central role in the pathogenesis of both IgAD and CVID.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> However, neither IgAD nor CVID can be attributed solely to a simple Mendelian trait and it seems that these diseases are the result of a complex interplay between a number of genes.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> However, associations of diseases with several immunological parameters and some genetic variants, especially <span class="elsevierStyleItalic">TNFRSF13B</span>, have been reported.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–23</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although defective class-switch recombination (CSR) is the main basis of hyper IgM (HIGM) syndrome, it has also been proposed as a basis for CVID and IgAD.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,25</span></a> CSR is an essential process which enables B cells to differentiate to class switched B cells and produce antibodies of different isotypes. Somatic hyper mutation is another essential process for affinity maturation of antibodies produced by B cells.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> Class switched memory B cells are decreased in some patients with CVID and also decreased levels of SHM have been reported in subsets of these patients.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Activation-induced cytidine deaminase (<span class="elsevierStyleItalic">AICDA</span>), a gene located at 12p13.31, is responsible for encoding a 198 amino-acid protein, named as AID.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30</span></a> Mutations in this gene have been previously reported to be the most frequent aberration among patients with autosomal recessive forms of HIGM,<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,30</span></a> a disease caused by defects in immunoglobulin CSR process and therefore presents with normal or elevated serum levels of IgM and low serum levels of IgG, IgA, and IgE.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27,31–34</span></a> AID also has been showed to be involved in SHM process.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27,29,30,35</span></a> Although the exact role of AID in CSR and SHM is not clear, two hypotheses of RNA-editing and DNA deamination have been proposed as possible mechanisms of action for AID.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,36–39</span></a> In both of them, AID exerts its action through cytidine deamination of cytidine to uracil and therefore changing the sequence of DNA or RNA.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Lower levels of AID expression in response to TGF-β, IFN-γ and IL-10 have been reported in B cells from patients with IgAD.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Recently, an association between rs2580874, an intronic SNP in <span class="elsevierStyleItalic">AICDA</span>, and IgAD and CVID has been reported.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Therefore, <span class="elsevierStyleItalic">AICDA</span> defects have been proposed as the underlying cause in a subset of patients with normal IgM levels or decreased SHM who represent a new subclass of patients with HIGM.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41,42</span></a> In order to evaluate the association of this SNP with IgAD/CVID, allele frequencies of this SNP were investigated in a group of patients with CVID and IgAD.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">Thirty-nine patients with CVID (21 male and 18 female) and nineteen patients with IgAD (10 male and 9 female), who referred to the main referral hospitals in Tehran, including Children's Medical Center, Rasoul-e-Akram Hospital, and Masih Daneshvari Hospital, were enrolled in this study as the patient group. The diagnosis of CVID and IgAD was based on standard criteria.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> Thirty-four healthy volunteers (20 male and 14 female) with the same ethnicity of the patients and without any history of severe infections and hospitalisation were also recruited as the control group to determine background population allele frequencies. They were all asymptomatic. This study was approved by the local Ethics Committee of the University. Written informed consents were taken from all the participants before sampling.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">SNP genotyping</span><p id="par0025" class="elsevierStylePara elsevierViewall">Five mL of peripheral blood was collected from all the participants in EDTA-treated tubes. Genomic DNA was extracted from peripheral blood leucocytes by proteinase K phenol–chloroform extraction method. We have determined the allele frequencies for one variant in intronic region of <span class="elsevierStyleItalic">AICDA</span> (<span class="elsevierStyleItalic">rs2580874</span>), using real-time PCR allelic discrimination TaqMan genotyping assays (Applied Biosystems, Foster city, USA) and ABI 7300 Real-Time PCR system. Reactions were processed following standard protocols for Applied Biosystems.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">Statistical analyses were done using ABI SDS V software, version 1.4. A <span class="elsevierStyleItalic">p</span>-value less than 0.05 was considered statistically significant. Odds ratios (OR) and 95% confidence intervals (95% CI) for the effect of all SNPs on IgAD/CVID risk were estimated.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Analysis of <span class="elsevierStyleItalic">AICDA</span> gene at <span class="elsevierStyleItalic">rs2580874</span> showed that the less frequent genotype in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Fourteen of 58 antibody deficient patients had AA genotype, which was insignificantly higher than the controls (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.23) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Indeed, the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.23).</p><p id="par0045" class="elsevierStylePara elsevierViewall">There was no significant difference on either GG or AA genotype between the two groups of CVID and IgAD (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.23).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">In this study, the contribution of one intronic SNP in <span class="elsevierStyleItalic">AICDA</span> gene was analysed toward susceptibility to IgAD and CVID, two heterogeneous group of disease which comprises two poles of hypogammaglubinaemia. In this study, we did not find any association between genotypes of this SNP with either IgAD or CVID.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In accordance to our results, no <span class="elsevierStyleItalic">AICDA</span> mutations have previously been reported in CVID patients.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> In a study on Danish patients no association was found between 7888 T/C in exon 4 of <span class="elsevierStyleItalic">AICDA</span> and CVID.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Although decreased levels of SHM and CSR are a pathological feature in some patients with IgAD and CVID, a block in differentiation of the mature B cell into a plasma cell is supposed to play a central role in the pathogenesis of both diseases.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,42</span></a> Patients with IgAD have normal quantities of IgA-bearing B-cell precursors and the majority of CVID patients have normal numbers of IgA, IgG, and IgM-bearing B cell precursors.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> So, in the majority of patients, B cells can normally undergo the CSR process.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Previously, a study on Swedish patients with CVID and IgAD found an association between this SNP and susceptibility to IgAD and CVID.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> By finding this association, Offer et al. suggested a hypothesis that a subset of patients with IgAD and CVID are predisposed to hypogammaglubinaemia due to variations in AID and they may be a new subclass of HIGM type 2.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Despite being in an untranslated region, they proposed that this SNP is linked to unidentified alleles, which may create splice variants or unstable mRNA or affect epigenetic modulation of AID expression.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Several reasons can explain the discordance between our results and the Swedish study. CVID and IgAD are highly heterogeneous and defects in multiple pathways may result in these phenotypes; so, variations in AID may be a risk factor for the disease in a subset of patients, who comprise a small percentage of our study population. In addition, the frequency of alleles in SNPs is highly dependent on ethnicity. Offer et al. also evaluated a larger population, which resulted in higher statistical power to detect the associations.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In summary, we found no association between the previously reported genetic variant in <span class="elsevierStyleItalic">AICDA</span> and development of CVID or IgAD. Despite our negative result, it is important to identify a possible association between CVID and IgAD and variations of genes involved in CSR, mismatch repair system and SHM. These studies may result in identification of the molecular basis of these diseases and classification of the patients into subgroups.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Further multi-center studies on a large number of patients are needed in this regard.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ethical disclosures</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Protection of human subjects and animals subjects</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Confidentiality of Data</span><p id="par0080" class="elsevierStylePara elsevierViewall">Confidentiality of Data. The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Right to privacy and informed consent</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres368103" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec347278" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "SNP genotyping" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Protection of human subjects and animals subjects" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Confidentiality of Data" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Right to privacy and informed consent" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interest" ] 8 => array:2 [ "identificador" => "xack92175" "titulo" => "Acknowledgement" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-01-13" "fechaAceptado" => "2013-02-26" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec347278" "palabras" => array:5 [ 0 => "Common variable immunodeficiency" 1 => "IgA deficiency" 2 => "Genetic susceptibility" 3 => "Single nucleotide polymorphism" 4 => "Activation induced cytidine deaminase" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of <span class="elsevierStyleItalic">AICDA</span> gene with PADs, this study was performed to evaluate such an association in Iranian patients.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in <span class="elsevierStyleItalic">AICDA</span> (<span class="elsevierStyleItalic">rs2580874</span>), using real-time PCR genotyping assay.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The less frequent genotype of <span class="elsevierStyleItalic">AICDA</span> in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There was no significant association between the previously reported genetic variant of <span class="elsevierStyleItalic">AICDA</span> gene and the development of CVID or IgAD, but further multi-center studies are also needed.</p>" ] ] "multimedia" => array:2 [ 0 => 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alleles \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">Controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>34) \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 " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">IgAD (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>19) <span class="elsevierStyleItalic">vs.</span> controls</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">CVID (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>39) <span class="elsevierStyleItalic">vs.</span> controls</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">IgAD <span class="elsevierStyleItalic">vs.</span> CVID (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>58)</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="" 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">Frequency \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"><span class="elsevierStyleItalic">p</span> value \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">OR (95%CI) \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">Frequency \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"><span class="elsevierStyleItalic">p</span> value \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">OR (95%CI) \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">Frequency \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"><span class="elsevierStyleItalic">p</span> value \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">OR (95%CI) \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">AA \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (38.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10.5%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 (0.03–1.09) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (30.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.67 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.72 (0.24–2.11) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (24.1%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.78 (0.66–27.92) \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">AG \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (52.9%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (63.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.67 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.52 (0.42–5.64) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (51.3%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.93 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.94 (0.34–2.68) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (55.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.57 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61 (0.17–2.16) \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">GG \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (8.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (26.3%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.69 (0.63–23.31) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (17.9%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.32 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.26 (0.46–12.28) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (20.7%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.50 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61 (0.14–2.73) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab553486.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Genotype frequencies of <span class="elsevierStyleItalic">AICDA</span> gene at <span class="elsevierStyleItalic">rs2580874</span> in patients with CVID, IgAD, and control individuals.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">SNP \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">Primary antibody deficiencies (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>58) \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">Controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>34) \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"><span class="elsevierStyleItalic">p</span> value \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">OR (95%CI) \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">AA \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (24.1%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (38.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.23 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.51 (0.19–1.41) \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">AG \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (55.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (52.9%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.99 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.09 (0.43–2.79) \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">GG \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (20.7%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (8.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.23 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.70 (0.63–13.19) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab553487.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Comparison of genotype frequencies of <span class="elsevierStyleItalic">AICDA</span> gene at rs2580874 between group of patients with primary antibody deficiencies and control group.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:43 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Rezaei" 1 => "A. Aghamohammadi" 2 => "M. Moin" 3 => "Z. Pourpak" 4 => "M. Movahedi" 5 => "M. Gharagozlou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10875-006-9047-x" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2006" "volumen" => "26" "paginaInicial" => "519" "paginaFinal" => "532" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17024564" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Aghamohammadi" 1 => "A. Farhoudi" 2 => "M. Moin" 3 => "N. Rezaei" 4 => "A. Kouhi" 5 => "Z. Pourpak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/CDLI.12.7.825-832.2005" "Revista" => array:6 [ "tituloSerie" => "Clin Diagn Lab Immunol" "fecha" => "2005" "volumen" => "12" "paginaInicial" => "825" "paginaFinal" => "832" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16002630" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Common variable immunodeficiency: a heterogeneous group needs further subclassification" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Aghamohammadi" 1 => "N. Parvaneh" 2 => "N. Rezaei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/eci.09.65" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Clin Immunol" "fecha" => "2009" "volumen" => "5" "paginaInicial" => "629" "paginaFinal" => "631" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20477686" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Common variable immunodeficiency: clinical and immunological features of 248 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Cunningham-Rundles" 1 => "C. Bodian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/clim.1999.4725" "Revista" => array:7 [ "tituloSerie" => "Clin Immunol" "fecha" => "1999" "volumen" => "92" "paginaInicial" => "34" "paginaFinal" => "48" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10413651" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0211139X11000886" "estado" => "S300" "issn" => "0211139X" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of immunoglobulin levels and infection rate in patients with common variable immunodeficiency after immunoglobulin replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Salehzadeh" 1 => "A. Aghamohammadi" 2 => "N. Rezaei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1684-1182(10)60002-3" "Revista" => array:6 [ "tituloSerie" => "J Microbiol Immunol Infect" "fecha" => "2010" "volumen" => "43" "paginaInicial" => "11" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20434118" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IgA deficiency: correlation between clinical and immunological phenotypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Aghamohammadi" 1 => "T. Cheraghi" 2 => "M. Gharagozlou" 3 => "M. Movahedi" 4 => "N. Rezaei" 5 => "M. Yeganeh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10875-008-9229-9" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "130" "paginaFinal" => "136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18683032" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetics of IgA deficiency and common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.W. Schroeder Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1385/CRIAI:19:2:127" "Revista" => array:6 [ "tituloSerie" => "Clin Rev Allergy Immunol" "fecha" => "2000" "volumen" => "19" "paginaInicial" => "127" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11107498" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progression of selective IgA deficiency to common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Aghamohammadi" 1 => "J. Mohammadi" 2 => "N. Parvaneh" 3 => "N. Rezaei" 4 => "M. Moin" 5 => "T. Espanol" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000135694" "Revista" => array:6 [ "tituloSerie" => "Int Arch Allergy Immunol" "fecha" => "2008" "volumen" => "147" "paginaInicial" => "87" "paginaFinal" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18520152" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IgA deficiency: clinical correlates and responses to pneumococcal vaccine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Edwards" 1 => "S. Razvi" 2 => "C. Cunningham-Rundles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2003.12.005" "Revista" => array:7 [ "tituloSerie" => "Clin Immunol" "fecha" => "2004" "volumen" => "111" "paginaInicial" => "93" "paginaFinal" => "97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15093556" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1699258X11001859" "estado" => "S300" "issn" => "1699258X" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1) haplotype" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Mohammadi" 1 => "R. Ramanujam" 2 => "S. Jarefors" 3 => "N. Rezaei" 4 => "A. Aghamohammadi" 5 => "P.K. Gregersen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10875-009-9336-2" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2010" "volumen" => "30" "paginaInicial" => "138" "paginaFinal" => "143" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19834793" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.W. Schroeder Jr." 1 => "Z.B. Zhu" 2 => "R.E. March" 3 => "R.D. Campbell" 4 => "S.M. Berney" 5 => "S.A. Nedospasov" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mol Med" "fecha" => "1998" "volumen" => "4" "paginaInicial" => "72" "paginaFinal" => "86" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9508785" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-6 gene variation in Spanish patients with immunoglobulin-A deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Lopez-Mejias" 1 => "A. Martinez" 2 => "N. Del Pozo" 3 => "M. Fernandez-Arquero" 4 => "A. Ferreira" 5 => "E. Urcelay" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.humimm.2008.02.002" "Revista" => array:6 [ "tituloSerie" => "Hum Immunol" "fecha" => "2008" "volumen" => "69" "paginaInicial" => "301" "paginaFinal" => "305" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18486766" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mannose-binding lectin polymorphisms in common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Aghamohammadi" 1 => "F. Foroughi" 2 => "N. Rezaei" 3 => "S. Dianat" 4 => "G. Solgi" 5 => "A.A. Amirzargar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10238-009-0049-x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Med" "fecha" => "2009" "volumen" => "9" "paginaInicial" => "285" "paginaFinal" => "290" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19408100" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N. Rezaei" 1 => "A.A. Amirzargar" 2 => "Y. Shakiba" 3 => "M. Mahmoudi" 4 => "B. Moradi" 5 => "A. Aghamohammadi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2249.2008.03790.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2009" "volumen" => "155" "paginaInicial" => "21" "paginaFinal" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19076825" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q. Pan-Hammarstrom" 1 => "U. Salzer" 2 => "L. Du" 3 => "J. Bjorkander" 4 => "C. Cunningham-Rundles" 5 => "D.L. Nelson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng0407-429" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2007" "volumen" => "39" "paginaInicial" => "429" "paginaFinal" => "430" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17392797" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytokine gene polymorphisms in common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Rezaei" 1 => "A. Aghamohammadi" 2 => "Y. Shakiba" 3 => "M. Mahmoudi" 4 => "A. Jalali" 5 => "B. Moradi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000210374" "Revista" => array:6 [ "tituloSerie" => "Int Arch Allergy Immunol" "fecha" => "2009" "volumen" => "150" "paginaInicial" => "1" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19339796" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel mutations in TACI (TNFRSF13B) causing common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Mohammadi" 1 => "C. Liu" 2 => "A. Aghamohammadi" 3 => "A. Bergbreiter" 4 => "L. Du" 5 => "J. Lu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10875-009-9317-5" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "777" "paginaFinal" => "785" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19629655" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "T-helper 1 and 2 cytokine assay in patients with common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N. Rezaei" 1 => "A. Aghamohammadi" 2 => "G.A. Kardar" 3 => "M. Nourizadeh" 4 => "Z. Pourpak" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Investig Allergol Clin Immunol" "fecha" => "2008" "volumen" => "18" "paginaInicial" => "449" "paginaFinal" => "453" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19123436" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytokine production by activated T cells in common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Rezaei" 1 => "A. Aghamohammadi" 2 => "M. Nourizadeh" 3 => "G.A. Kardar" 4 => "Z. Pourpak" 5 => "A. Zare" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Investig Allergol Clin Immunol" "fecha" => "2010" "volumen" => "20" "paginaInicial" => "244" "paginaFinal" => "251" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20635790" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum bactericidal antibody responses to meningococcal polysaccharide vaccination as a basis for clinical classification of common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Rezaei" 1 => "A. Aghamohammadi" 2 => "S.D. Siadat" 3 => "M. Moin" 4 => "Z. Pourpak" 5 => "M. Nejati" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/CVI.00489-07" "Revista" => array:6 [ "tituloSerie" => "Clin Vaccine Immunol" "fecha" => "2008" "volumen" => "15" "paginaInicial" => "607" "paginaFinal" => "611" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18235041" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased serum levels of soluble CD30 in patients with common variable immunodeficiency and its clinical implications" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N. Rezaei" 1 => "M. Haji-Molla-Hoseini" 2 => "A. Aghamohammadi" 3 => "A.A. Pourfathollah" 4 => "M. Moghtadaie" 5 => "Z. Pourpak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10875-007-9135-6" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2008" "volumen" => "28" "paginaInicial" => "78" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17912490" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum bactericidal antibody response 1 year after meningococcal polysaccharide vaccination of patients with common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Rezaei" 1 => "S.D. Siadat" 2 => "A. Aghamohammadi" 3 => "M. Moin" 4 => "Z. Pourpak" 5 => "D. Norouzian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/CVI.00389-09" "Revista" => array:6 [ "tituloSerie" => "Clin Vaccine Immunol" "fecha" => "2010" "volumen" => "17" "paginaInicial" => "524" "paginaFinal" => "528" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20106999" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "B-cell–T-cell activation and interaction in common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Rezaei" 1 => "J.B. Wing" 2 => "A. Aghamohammadi" 3 => "J. Carlring" 4 => "A. Lees" 5 => "H. Asgarian-Omran" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.humimm.2010.01.019" "Revista" => array:6 [ "tituloSerie" => "Hum Immunol" "fecha" => "2010" "volumen" => "71" "paginaInicial" => "355" "paginaFinal" => "362" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20097245" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of switched memory B cells in patients with IgA deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Aghamohammadi" 1 => "H. Abolhassani" 2 => "M. Biglari" 3 => "S. Abolmaali" 4 => "K. Moazzami" 5 => "M. Tabatabaeiyan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000323903" "Revista" => array:6 [ "tituloSerie" => "Int Arch Allergy Immunol" "fecha" => "2011" "volumen" => "156" "paginaInicial" => "462" "paginaFinal" => "468" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21832837" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of class-switched memory B cells in patients with common variable immunodeficiency and its clinical implications" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Vodjgani" 1 => "A. Aghamohammadi" 2 => "M. Samadi" 3 => "M. Moin" 4 => "J. Hadjati" 5 => "M. Mirahmadian" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Investig Allergol Clin Immunol" "fecha" => "2007" "volumen" => "17" "paginaInicial" => "321" "paginaFinal" => "328" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17982925" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel mutation of the activation-induced cytidine deaminase gene in a Tajik family: special review on hyper-immunoglobulin M syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.A. Mahdaviani" 1 => "A. Hirbod-Mobarakeh" 2 => "N. Wang" 3 => "A. Aghamohammadi" 4 => "L. Hammarstrom" 5 => "M.R. Masjedi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/eci.12.46" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Clin Immunol" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "539" "paginaFinal" => "546" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22992148" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on the hyper immunoglobulin M syndromes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E.G. Davies" 1 => "A.J. Thrasher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2141.2010.08077.x" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2010" "volumen" => "149" "paginaInicial" => "167" "paginaFinal" => "180" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20180797" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Altered spectrum of somatic hypermutation in common variable immunodeficiency disease characteristic of defective repair of mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Duvvuri" 1 => "V.R. Duvvuri" 2 => "J. Grigull" 3 => "A. Martin" 4 => "Q. Pan-Hammarstrom" 5 => "G.E. Wu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00251-010-0483-7" "Revista" => array:6 [ "tituloSerie" => "Immunogenetics" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "1" "paginaFinal" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20938659" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Muramatsu" 1 => "V.S. Sankaranand" 2 => "S. Anant" 3 => "M. Sugai" 4 => "K. Kinoshita" 5 => "N.O. Davidson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "1999" "volumen" => "274" "paginaInicial" => "18470" "paginaFinal" => "18476" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10373455" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Revy" 1 => "T. Muto" 2 => "Y. Levy" 3 => "F. Geissmann" 4 => "A. Plebani" 5 => "O. Sanal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2000" "volumen" => "102" "paginaInicial" => "565" "paginaFinal" => "575" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11007475" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Aghamohammadi" 1 => "N. Parvaneh" 2 => "N. Rezaei" 3 => "K. Moazzami" 4 => "S. Kashef" 5 => "H. Abolhassani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10875-009-9315-7" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "769" "paginaFinal" => "776" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19575287" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Isolated growth hormone deficiency in a patient with immunoglobulin class switch recombination deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Kashef" 1 => "M.M. Ghaedian" 2 => "N. Rezaei" 3 => "Z. Karamizadeh" 4 => "A. Aghamohammadi" 5 => "A. Durandy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Investig Allergol Clin Immunol" "fecha" => "2009" "volumen" => "19" "paginaInicial" => "233" "paginaFinal" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19610268" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Quartier" 1 => "J. Bustamante" 2 => "O. Sanal" 3 => "A. Plebani" 4 => "M. Debre" 5 => "A. Deville" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2003.10.007" "Revista" => array:6 [ "tituloSerie" => "Clin Immunol" "fecha" => "2004" "volumen" => "110" "paginaInicial" => "22" "paginaFinal" => "29" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14962793" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N. Rezaei" 1 => "A. Aghamohammadi" 2 => "A. Ramyar" 3 => "Q. Pan-Hammarstrom" 4 => "L. Hammarstrom" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000142050" "Revista" => array:6 [ "tituloSerie" => "Int Arch Allergy Immunol" "fecha" => "2008" "volumen" => "147" "paginaInicial" => "255" "paginaFinal" => "259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18594157" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel activation-induced cytidine deaminase gene mutation in a Tunisian family with hyper IgM syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Fiorini" 1 => "S. Jilani" 2 => "C.G. Losi" 3 => "A. Silini" 4 => "S. Giliani" 5 => "S. Ferrari" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00431-004-1540-8" "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "2004" "volumen" => "163" "paginaInicial" => "704" "paginaFinal" => "708" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15372234" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V. Shivarov" 1 => "R. Shinkura" 2 => "T. Honjo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0806641105" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2008" "volumen" => "105" "paginaInicial" => "15866" "paginaFinal" => "15871" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18832469" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "De novo protein synthesis is required for activation-induced cytidine deaminase-dependent DNA cleavage in immunoglobulin class switch recombination" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N.A. Begum" 1 => "K. Kinoshita" 2 => "M. Muramatsu" 3 => "H. Nagaoka" 4 => "R. Shinkura" 5 => "T. Honjo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0405219101" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2004" "volumen" => "101" "paginaInicial" => "13003" "paginaFinal" => "13007" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15317942" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular mechanism for generation of antibody memory" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Shivarov" 1 => "R. Shinkura" 2 => "T. Doi" 3 => "N.A. Begum" 4 => "H. Nagaoka" 5 => "I.M. Okazaki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1098/rstb.2008.0183" "Revista" => array:6 [ "tituloSerie" => "Philos Trans R Soc Lond B Biol Sci" "fecha" => "2009" "volumen" => "364" "paginaInicial" => "569" "paginaFinal" => "575" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19022739" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AID mutates <span class="elsevierStyleItalic">E. coli</span> suggesting a DNA deamination mechanism for antibody diversification" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.K. Petersen-Mahrt" 1 => "R.S. Harris" 2 => "M.S. Neuberger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature00862" "Revista" => array:7 [ "tituloSerie" => "Nature" "fecha" => "2002" "volumen" => "418" "paginaInicial" => "99" "paginaFinal" => "103" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12097915" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0211139X08735741" "estado" => "S300" "issn" => "0211139X" ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Class switch recombination in selective IgA-deficient subjects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Hummelshoj" 1 => "L.P. Ryder" 2 => "L.K. Nielsen" 3 => "C.H. Nielsen" 4 => "L.K. Poulsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2249.2006.03096.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2006" "volumen" => "144" "paginaInicial" => "458" "paginaFinal" => "466" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16734615" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unique DNA repair gene variations and potential associations with the primary antibody deficiency syndromes IgAD and CVID" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.M. Offer" 1 => "Q. Pan-Hammarstrom" 2 => "L. Hammarstrom" 3 => "R.S. Harris" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0012260" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2010" "volumen" => "5" "paginaInicial" => "e12260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20805886" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Normal ICOS, ICOSL and AID alleles in Danish patients with common variable immunodeficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Ohm-Laursen" 1 => "L. Schjebel" 2 => "K. Jacobsen" 3 => "H. Permin" 4 => "A. Svejgaard" 5 => "T. Barington" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-3083.2005.001603.x" "Revista" => array:6 [ "tituloSerie" => "Scand J Immunol" "fecha" => "2005" "volumen" => "61" "paginaInicial" => "566" "paginaFinal" => "574" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15963052" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.E. Conley" 1 => "L.D. Notarangelo" 2 => "A. Etzioni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/clim.1999.4799" "Revista" => array:6 [ "tituloSerie" => "Clin Immunol" "fecha" => "1999" "volumen" => "93" "paginaInicial" => "190" "paginaFinal" => "197" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10600329" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack92175" "titulo" => "Acknowledgement" "texto" => "<p id="par0095" class="elsevierStylePara elsevierViewall">This study was supported by a grant (<span class="elsevierStyleGrantNumber" refid="gs0005">90-03-30-13868</span>) from <span class="elsevierStyleGrantSponsor" id="gs0005">Tehran University of Medical Sciences</span>.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004200000005/v1_201409050044/S030105461300102X/v1_201409050044/en/main.assets" "Apartado" => array:4 [ "identificador" => "5554" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000004200000005/v1_201409050044/S030105461300102X/v1_201409050044/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030105461300102X?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 1 | 4 |
| 2024 October | 10 | 8 | 18 |
| 2024 September | 28 | 10 | 38 |
| 2024 August | 17 | 4 | 21 |
| 2024 July | 9 | 7 | 16 |
| 2024 June | 14 | 5 | 19 |
| 2024 May | 11 | 11 | 22 |
| 2024 April | 13 | 8 | 21 |
| 2024 March | 18 | 8 | 26 |
| 2024 February | 20 | 7 | 27 |
| 2024 January | 405 | 11 | 416 |
| 2023 December | 15 | 21 | 36 |
| 2023 November | 20 | 7 | 27 |
| 2023 October | 14 | 8 | 22 |
| 2023 September | 20 | 5 | 25 |
| 2023 August | 16 | 9 | 25 |
| 2023 July | 17 | 9 | 26 |
| 2023 June | 27 | 2 | 29 |
| 2023 May | 56 | 5 | 61 |
| 2023 April | 40 | 7 | 47 |
| 2023 March | 41 | 5 | 46 |
| 2023 February | 16 | 6 | 22 |
| 2023 January | 9 | 9 | 18 |
| 2022 December | 9 | 12 | 21 |
| 2022 November | 10 | 2 | 12 |
| 2022 October | 25 | 7 | 32 |
| 2022 September | 16 | 13 | 29 |
| 2022 August | 9 | 10 | 19 |
| 2022 July | 8 | 10 | 18 |
| 2022 June | 13 | 10 | 23 |
| 2022 May | 27 | 9 | 36 |
| 2022 April | 12 | 13 | 25 |
| 2022 March | 33 | 10 | 43 |
| 2022 February | 26 | 3 | 29 |
| 2022 January | 36 | 12 | 48 |
| 2021 December | 24 | 11 | 35 |
| 2021 November | 11 | 9 | 20 |
| 2021 October | 13 | 12 | 25 |
| 2021 September | 12 | 10 | 22 |
| 2021 August | 6 | 6 | 12 |
| 2021 July | 15 | 13 | 28 |
| 2021 June | 12 | 11 | 23 |
| 2021 May | 17 | 21 | 38 |
| 2021 April | 17 | 11 | 28 |
| 2021 March | 10 | 13 | 23 |
| 2021 February | 14 | 9 | 23 |
| 2021 January | 17 | 12 | 29 |
| 2020 December | 2 | 0 | 2 |
| 2020 November | 0 | 1 | 1 |
| 2020 October | 0 | 2 | 2 |
| 2020 August | 0 | 1 | 1 |
| 2020 July | 0 | 1 | 1 |
| 2020 June | 0 | 1 | 1 |
| 2020 May | 0 | 1 | 1 |
| 2020 April | 0 | 2 | 2 |
| 2020 March | 0 | 1 | 1 |
| 2020 January | 0 | 2 | 2 |
| 2019 December | 0 | 3 | 3 |
| 2019 September | 0 | 1 | 1 |
| 2019 July | 0 | 6 | 6 |
| 2019 June | 0 | 3 | 3 |
| 2019 May | 0 | 16 | 16 |
| 2018 March | 6 | 0 | 6 |
| 2018 February | 10 | 1 | 11 |
| 2018 January | 12 | 0 | 12 |
| 2017 December | 3 | 1 | 4 |
| 2017 November | 9 | 5 | 14 |
| 2017 October | 9 | 3 | 12 |
| 2017 September | 8 | 1 | 9 |
| 2017 August | 9 | 1 | 10 |
| 2017 July | 5 | 3 | 8 |
| 2017 June | 16 | 4 | 20 |
| 2017 May | 17 | 4 | 21 |
| 2017 April | 18 | 1 | 19 |
| 2017 March | 21 | 4 | 25 |
| 2017 February | 20 | 5 | 25 |
| 2017 January | 17 | 5 | 22 |
| 2016 December | 27 | 8 | 35 |
| 2016 November | 21 | 3 | 24 |
| 2016 October | 27 | 9 | 36 |
| 2016 September | 19 | 6 | 25 |
| 2016 August | 17 | 4 | 21 |
| 2016 July | 10 | 1 | 11 |
| 2016 June | 19 | 7 | 26 |
| 2016 May | 12 | 6 | 18 |
| 2016 April | 11 | 14 | 25 |
| 2016 March | 17 | 15 | 32 |
| 2016 February | 10 | 20 | 30 |
| 2016 January | 13 | 22 | 35 |
| 2015 December | 17 | 16 | 33 |
| 2015 November | 6 | 9 | 15 |
| 2015 October | 25 | 17 | 42 |
| 2015 September | 12 | 15 | 27 |
| 2015 June | 0 | 1 | 1 |
| 2015 May | 0 | 2 | 2 |
| 2015 March | 0 | 3 | 3 |
| 2015 February | 0 | 3 | 3 |
| 2015 January | 0 | 3 | 3 |
| 2014 November | 1 | 8 | 9 |
| 2014 October | 0 | 1 | 1 |
| 2014 September | 2 | 4 | 6 |
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