Selective IgA Deficiency in Autoimmune Diseases

Wang, Ning; Shen, Nan; Vyse, Timothy J.; Anand, Vidya; Gunnarson, Iva; Sturfelt, Gunnar; Rantapää-Dahlqvist, Solbritt; Elvin, Kerstin; Truedsson, Lennart; Åndersson, Bengt; Dahle, Charlotte; Örtqvist, Eva; Gregersen, Peter K.; Behrens, Timothy W.; Hammarström, Lennart

doi:10.2119/molmed.2011.00195

Cited by 174 publications

(139 citation statements)

References 199 publications

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“…However, some cases may be characterized with recurrent infections, allergic conditions, and autoimmune complications [8,98,99,100]. Since 30% of sIgAD patients have considerable titers of IgG antibodies against IgA, a breakdown of tolerance against IgA itself or against other factors that contribute to the class switching process, such as TACI, APRIL, and BAFF, probably accounts for the pathophysiological mechanism [101,102,103,104]. Evidence in support of this hypothesis includes that the pathogenesis of sIgAD is an autoimmune process [105].…”

Section: Autoimmunity In Padsmentioning

confidence: 99%

“…A significant correlation with the MHC polymorphic region has also been reported. Furthermore, non-MHC genes, including interferon-induced helicase 1 ( IFIH1 ) and c-type lectin domain family 16 member A ( CLEC16A ), have been reported to have association with sIgAD development and some of the above-mentioned autoimmune diseases [101]. Apart from the genetic susceptibility, the failure of antigen clearance from mucosal surfaces with resultant immune complex deposition is also hypothesized to induce autoimmune disease in IgAD.…”

Section: Autoimmunity In Padsmentioning

confidence: 99%

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Autoimmunity in Primary Antibody Deficiencies

Azizi¹,

Ahmadi²,

Abolhassani³

et al. 2016

Int Arch Allergy Immunol

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Primary antibody deficiencies (PADs) are the most common inherited primary immunodeficiencies in humans, characterized by hypogammaglobulinemia, an inability to produce specific antibodies, and recurrent infections mainly caused by encapsulated bacteria. However, it has been shown that inflammatory disorders, granulomatous lesions, lymphoproliferative diseases, cancer, and autoimmunity are associated with the various types of PAD. Both systemic and organ-specific autoimmune diseases could be attributed to B-cell defects in PAD patients. Immune thrombocytopenic purpura and autoimmune hemolytic anemia are the most common autoimmune disorders in this group of patients. The aim of this review is to describe the proposed mechanisms for autoimmunity and to review the literature with respect to the reported autoimmune disorders in each type of PAD.

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Section: Autoimmunity In Padsmentioning

confidence: 99%

Section: Autoimmunity In Padsmentioning

confidence: 99%

Autoimmunity in Primary Antibody Deficiencies

Azizi¹,

Ahmadi²,

Abolhassani³

et al. 2016

Int Arch Allergy Immunol

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“…Nevertheless, the concomitant expression of IgA and IgM is also associated with IgA deficiency, as shown by Conley and Cooper (1981) who described that 90 % of patients presenting an IgA + IgM + phenotype have a pathological blocker on IgA + B cell differentiation during the IgA-class switch. Selective IgA deficiency is associated with a higher prevalence of infections and a variety of concomitant autoimmune diseases, including Graves' disease, systemic lupus erythematosus, type 1 diabetes, celiac disease, myasthenia gravis and rheumatoid arthritis (Wang et al 2011). Galectin-3 plays a pro-inflammatory role exacerbating the effects in autoimmune disorders (Radosavljevic et al 2012), however the involvement of galectin-3 in IgA physiology is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Lack of galectin-3 up-regulates IgA expression by peritoneal B1 lymphocytes during B cell differentiation

et al. 2015

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Galectin-3 is a β-galactoside-binding protein with an inhibitory role in B cell differentiation into plasma cells in distinct lymphoid tissues. We use a model of chronic schistosomiasis, a well-characterized experimental disease hallmarked by polyclonal B cell activation, in order to investigate the role of galectin-3 in controlling IgA production through peritoneal B1 cells. Chronically infected, galectin-3-deficient mice (Lgals3 −/− ) display peritoneal fluid hypercellularity, increased numbers of atypical peritoneal IgM + /IgA + B1a and B1b lymphocytes and histological disturbances in plasma cell niches when compared with Lgals3 + / + mice. Similar to our infection model, peritoneal B1 cells from uninfected Lgals3 −/− mice show enhanced switching to IgA after in vitro treatment with interleukin-5 plus transforming growth factor-β (IL-5 + TGF-β1). A higher number of IgA + B1a lymphocytes was found in the peritoneal cavity of Lgals3 −/− -uninfected mice at 1 week after i.p. injection of IL-5 + TGF-β1; this correlates with the increased levels of secreted IgA detected in the peritoneal fluid of these mice after cytokine treatment. Interestingly, a higher number of degranulated mast cells is present in the peritoneal cavity of uninfected and Schistosoma mansoni-infected Lgals3 −/− mice, indicating that, at least in part, mast cells account for the enhanced differentiation of B1 into IgAproducing B cells found in the absence of galectin-3. Thus, a novel role is revealed for galectin-3 in controlling the expression of surface IgA by peritoneal B1 lymphocytes; this might have important implications for manipulating the mucosal immune response.

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“…In comparison with sIgAD, a humoral immunodeficiency also characterized by immune dysregulation with a higher coincidence of autoimmune diseases, the incidence of T1D is very well-characterized, with a 5-fold increase compared to the incidence in the general population [25]. CVID and sIgAD share some immunological background features, and sIgAD may progress to CVID in some patients; thus, a higher occurrence of T1D can be expected in CVID cohorts [26,27] .…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of T1D in sIgAD has been reported in many studies and varies from 0.5% (500/100,000) in Austria to 1.8% (1,800/100,000) in the UK [24]. Recent data from 2011 show an overall prevalence of T1D among sIgA patients of 1% (1,000/100,000) in a European Caucasian population and a roughly 5-fold-higher prevalence in sIgAD patients compared with the incidence in the general population [25]. In contrast, the association of T1D and XLA has only been described in 1 case report, which described a 14-year-old male patient who developed T1D 11 years after the diagnosis of XLA; this patient had severely impaired antibody production [8].…”

Section: Review Of Literature and Data From The Esid Registry Databasementioning

confidence: 99%

Negativity for Specific Autoantibodies in Patients with Type 1 Diabetes That Developed on a Background of Common Variable Immunodeficiency

Milota¹,

Šumnı́k

Obermannová

et al. 2015

Int Arch Allergy Immunol

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Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by disturbed antibody production and a dysregulated immune system. Aside from recurrent infections, the most common complications of CVID are autoimmune complications, particularly autoimmune cytopenias. To date, type 1 diabetes mellitus (T1D) in combination with CVID has only been described as an unusual complication in several reports, but the true incidence of T1D with CVID remains unknown. We describe 2 patients with a combination of T1D and CVID with serious impairment of antibody production. We also provide a review of the available literature. T1D-specific insulin autoantibodies and autoantibodies to glutamic acid decarboxylase and tyrosine phosphatase IA2 were not detected in either of our patients at the time of diagnosis or during the course of the disease. In both cases, T1D manifestation and diagnosis preceded the discovery of CVID by several years. Following the diagnosis of immunodeficiency and the start of immunoglobulin substitution therapy, their clinical status improved, manifesting as a lower frequency of infections and improved T1D control, with decreased glycosylated hemoglobin A1c values. Based on these reported cases, we assume that T1D might be more frequent than previously reported in patients with CVID. To verify the actual incidence of T1D among CVID patients, we searched the European Society for Immunodeficiencies Registry database, and found 25 cases of T1D in 1,671 listed CVID patients, suggesting a higher occurrence of T1D among CVID patients than previously thought. Early diagnosis and treatment of immunodeficiency improve both the prognosis and the course of CVID, reduce the frequency and severity of infections and may contribute to better management of T1D.

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Selective IgA Deficiency in Autoimmune Diseases

Cited by 174 publications

References 199 publications

Autoimmunity in Primary Antibody Deficiencies

Autoimmunity in Primary Antibody Deficiencies

Lack of galectin-3 up-regulates IgA expression by peritoneal B1 lymphocytes during B cell differentiation

Negativity for Specific Autoantibodies in Patients with Type 1 Diabetes That Developed on a Background of Common Variable Immunodeficiency

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