Association with IgG3 deficiency in chronic autoimmune neutropenia in adults: case report and literature review

Pardos-Gea, José; Artaza Miñano, Gonzalo; Sanjose, Antonio

doi:10.1016/j.medcle.2016.04.027

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Estudio de un caso y revisión bibliográfica" ] ] "textoCompleto" => "Autoimmune neutropenia,<a class="elsevierStyleCrossRef" href="#bib0055">1</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">2</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.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°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 (13mg/dl, normality: 22–288mg/dl), which repeated after 6 weeks, was confirmed.Neutropenia can accompany various immunodeficiencies with immunoglobulin deficiency or disorder.<a class="elsevierStyleCrossRef" href="#bib0065">3</a> The combined immunodeficiencies (Wiskott-Aldrich syndrome, ataxia-telangiectasia, X-linked hyper-IgM syndrome, severe combined immunodeficiency<a class="elsevierStyleCrossRef" href="#bib0070">4</a>) and X-linked agammaglobulinemia<a class="elsevierStyleCrossRef" href="#bib0075">5</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">6</a>IgG3 congenital deficiency is the rarest IgG subtype.<a class="elsevierStyleCrossRef" href="#bib0085">7</a> It is most frequently detected in adults, who may have recurrent respiratory infections typically by Moraxella sp., and recurrent skin infections such as erysipelas by Streptococcus pyogenes. 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">8</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">8</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">9</a> all of idiopathic etiology, showed significant decreased levels of IgG3 (p<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">9,10</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.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." 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ISSN: 2387-0206

Launched in 1943, Medicina Clínica is a fortnightly journal aimed at the promotion of clinical research and practice among internal medicine and other specialists. The key characteristics of Medicina Clínica are the scientific and methodological rigor of its manuscripts, the topicality of its contents, and, especially, its practical focus with highly useful information for clinical practice. Medicina Clínica is predominantly interested in publishing original research manuscripts, which are rigorously selected according to their quality, originality, and interest, and also in continued medical education-oriented manuscripts, which are commissioned by the journal to relevant authors (Editorials, Reviews, and Diagnosis and Treatment). These manuscripts contain updated topics with a major clinical or conceptual relevance in modern medicine. The journal adheres to the standards of academic research publications in all aspects including peer-review and ethical principles. Medicina Clínica is included in the General and Internal Medicine category of Thomson Reuters.

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Current Contents/Clinical Medicine, Journal Citation Reports, SCI-Expanded, Index Medicus/Medline, Excerpta Medica/EMBASE, IBECS, IME, MEDES, PASCAL, SCOPUS, SciVerse ScienceDirect

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Impact factor

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years.

© Clarivate Analytics, Journal Citation Reports 2022

Impact factor 2023

2.6

Citescore

CiteScore measures average citations received per document published.

Citescore 2023

3.1

SJR

SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact.

SJR 2023

0.371

SNIP

SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field.

SNIP 2023

0.511

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Journal Information

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Vol. 145. Issue 12.

Pages 553-554 (December 2015)

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