Letter to the Editor
Association with IgG3 deficiency in chronic autoimmune neutropenia in adults: case report and literature review
Neutropenia autoinmunitaria crónica del adulto y su frecuente asociación con déficit de IgG. Estudio de un caso y revisión bibliográfica
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Estudio de un caso y revisión bibliográfica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune neutropenia,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> defined by the presence of antineutrophil autoantibodies against various surface antigens, mostly with Fc receptor function, accounts for 30% of chronic neutropenia in adults<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and can be primary or secondary to autoimmune diseases (rheumatoid arthritis-Felty syndrome, SLE, Sjögren's syndrome), infectious diseases (HIV, parvovirus B19) or neoplastic diseases (Wilms tumor, large granular lymphocytic leukemia). Most patients will have mild chronic neutropenia (1000–1500/μl), with a benign clinical course where only 10–20% will have recurrent infections, usually bacterial respiratory infections, abscesses or fever of unknown source, requiring only antibiotic treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 55 year old male with no toxic habits, with a history of surgical intervention for lumbar herniated disk and prostatitis a year before the current visit, with proper evolution. The patient had been referred from the general practitioner to Hematology due to neutropenia. Since 2009, with no previous blood counts, the patient suffered from leukopenia with mild neutropenia, with an overall neutrophil count ranging from 1000 to 1500/μl, with normal red cells and platelets. Apart from the medical history reported, the patient had no recurrent infectious processes in pediatric or adult stage. Hematology confirmed positive antineutrophil antibodies in direct study. Large granular lymphocytic leukemia and other lymphoproliferative disorders were ruled out by extension and immunophenotyping of peripheral blood cells, and the normality of vitamin maturation factors was verified. The patient was referred to Internal Medicine to assess clinical entities associated to autoimmune neutropenia, as well as the recent onset of fever. The patient had reported episodes of fever up to 38<span class="elsevierStyleHsp" style=""></span>°C for a month, without bacteremia or cyclical basis, once or twice a week. Intermittent rectal bleeding was associated. The patient underwent a colonoscopy, which was normal, and abdominal CT scan, showing diverticulosis. On examination, the patient reported left iliac fossa pain in one of the visits. Therefore, he initiated treatment with empirical use of ciprofloxacin and metronidazole, focusing on diverticulitis, obtaining clinical remission. The study of autoimmune neutropenia was completed, and systemic autoimmune entities were ruled out (lack of clinical criteria, negative for ANA, ENA, rheumatoid factor, anti-tissue antibodies), as well as infections (HIV-negative and parvovirus B19-negative). Finally, studying the causes of autoimmune neutropenia, occurrence of humoral immunity disorders or dysgammaglobulinemias was assessed. Proteinogram and plasma concentration of total IgG, IgM and IgA were normal, but there was isolated IgG3 subclass deficiency (13<span class="elsevierStyleHsp" style=""></span>mg/dl, normality: 22–288<span class="elsevierStyleHsp" style=""></span>mg/dl), which repeated after 6 weeks, was confirmed.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Neutropenia can accompany various immunodeficiencies with immunoglobulin deficiency or disorder.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The combined immunodeficiencies (Wiskott-Aldrich syndrome, ataxia-telangiectasia, X-linked hyper-IgM syndrome, severe combined immunodeficiency<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a>) and X-linked agammaglobulinemia<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> begin in childhood with severe hypogammaglobulinemias and neutropenia of diverse etiologies (autoimmune, infectious, bone marrow deficiency). The common variable, as most common immunodeficiency in the adult population, occurs along with neutropenia, being usually autoinmune.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">IgG3 congenital deficiency is the rarest IgG subtype.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> It is most frequently detected in adults, who may have recurrent respiratory infections typically by <span class="elsevierStyleItalic">Moraxella</span> sp., and recurrent skin infections such as erysipelas by <span class="elsevierStyleItalic">Streptococcus pyogenes</span>. Patients with IgG3 congenital deficiency would not have higher prevalence of neutropenia according to the few cases reported to date.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> However, studies evaluating populations with chronic neutropenia in adults, of any etiology, have reported IgG3 deficiency was frequently associated. Karlström et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> analyzed 30 patients with chronic neutropenia in adults (with 8 cases of autoimmune cause) and almost half of them with IgG3 deficiency associated (47% patients), a phenomenon that remained over a long period of years of follow up. The infection rate was similar in those with or without IgG3 deficiency. Another study with 83 patients with chronic neutropenia in adults,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> all of idiopathic etiology, showed significant decreased levels of IgG3 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) compared to the control group, in addition to increased IgA in those with more severe neutropenia. Regarding the possible explanation for this association, 2 studies<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> showed how in idiopathic forms of chronic neutropenia, considered a myelodysplastic syndrome of the granulocyte progenitors, patients had elevated levels of serum TGFB1. In addition, mesenchymal stem cells of bone marrow produced excessive TGFB1; we know that this cytokine may decrease IgG3 production and increase isotype switching to IgA in B cells. No similar pathophysiological studies are available on autoimmune forms of chronic neutropenia.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion, we have verified through the description of a case and literature review that: (a) chronic neutropenia in adults of any etiology, in our case, autoimmune, may be accompanied by an isolated IgG3 deficiency; (b) it will not change the clinical course of these patients who remain generally indolent, with low prevalence of recurrent infections, and; (c) it will probably be secondary to changes in the immune profile of cytokine secretion (increased TGFB1) which may accompany chronic neutropenia, although this pathophysiological explanation based on idiopathic forms has not been corroborated in chronic autoimmune neutropenia.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pardos-Gea J, Artaza Miñano G, Sanjose A. Neutropenia autoinmunitaria crónica del adulto y su frecuente asociación con déficit de IgG. Estudio de un caso y revisión bibliográfica. Med Clin (Barc). 2015;145:553–554.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic autoimmune neutropenia due to anti-NA2 antibody" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Lalezari" 1 => "A.F. Jiang" 2 => "L. Yegen" 3 => "M. 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