Monogenic mutations associated with IgA deficiency

Abolhassani, Hassan; Aghamohammadi, Asghar; Hammarström, Lennart

doi:10.1080/1744666x.2016.1198696

Cited by 30 publications

(30 citation statements)

References 95 publications

(3 reference statements)

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“…SIgAD is the most prevalent primary immunodeficiency, found at the highest frequency of 1 in 142 in Caucasians, and a low of 1 in 18,550 among Japanese, with a prevalence among other ethnicities ranging between these values. [1,3,[10][11][12][13] Genetic factors likely play a role in the development of SIgAD, as 33.3% of patients are from consanguineous unions. [1] The disease does not follow simple mendelian inheritance patterns, but does exhibit familial clustering.…”

Section: Epidemiologymentioning

confidence: 99%

“…Researchers have observed that certain primary immunodeficiency syndromes are secondary to monogenic mutations that predispose the same patients to autoimmune manifestations. [10] Bronson and colleagues noted several monogenic associations between SIgAD and autoimmune disease in a genomewide study. [60] Another paper found a similar variant of CTLA4-ICOS common in celiac disease, SIgAD, and CVID.…”

Section: Mechanisms Of Autoimmunity In Iga Deficiencymentioning

confidence: 99%

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The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency

Odineal

Gershwin

2019

Clinic Rev Allerg Immunol

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Selective Immunoglobulin A Deficiency (SIgAD) is the most common primary immunodeficiency, defined as an isolated deficiency of IgA (less than 0.07 g/L). Although the majority of people born with IgA deficiency lead normal lives without significant pathology, there is nonetheless a significant association of IgA deficiency with mucosal infection, increased risks of atopic disease, and a higher prevalence of autoimmune disease. To explain these phenomena, we have performed an extensive literature review to define the geoepidemiology of IgA deficiency and particularly the relative risks for developing Systemic Lupus Erythematosus, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, Crohn's Disease, ulcerative colitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and vitiligo; these diseases have strong data to support an association. We also note weaker associations with scleroderma, celiac disease, autoimmune hepatitis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia. Minimal if any associations are noted with myasthenia gravis, lichen planus, and multiple sclerosis. Finally, more recent data provide clues on the possible immunologic mechanisms that lead to the association of IgA deficiency and autoimmunity; these lessons are important for understanding the etiology of autoimmune disease. 2 3 Introduction:

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Section: Epidemiologymentioning

confidence: 99%

Section: Mechanisms Of Autoimmunity In Iga Deficiencymentioning

confidence: 99%

The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency

Odineal

Gershwin

2019

Clinic Rev Allerg Immunol

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“…It has also been demonstrated that some responsible genes in the B cell receptor (BCR) signaling, like BTK and transmembrane activator and CAML interactor , are modifying factors in a number of IgAD individuals. There are some other reported non-MHC gene mutations in immune disorders who had IgAD (Table 1) [15, 37]. Non-MHC loci polymorphism of some genes listed in Table 1 have been reported to be associated with SIgAD [38].…”

Section: Pathogenesis Of Sigadmentioning

confidence: 99%

“…Except for the predefined paradigm of cytogenetic abnormalities (e.g., 4p monosomy, trisomy 8, trisomy 10p, translocation of 10q to 4p, 17p11.2 deletions, 18q-syndrome, trisomy 21, monosomy 22, and 22q11.2 deletion syndrome) [15] and HLA haplotypes association for SIgAD pathogenesis, monogenic mutations should be considered as a separate etiology [13]. The strategy to classify IgA-deficient patients in homogenized groups will be helpful in SIgAD pathogenesis, besides taking an imbalanced genetic approach using high-throughput sequencing.…”

Section: Pathogenesis Of Sigadmentioning

confidence: 99%

“…Based on the several efforts to clarify the etiology and pathogenesis of SIgAD, the major problem is the failure of B lymphocyte to produce IgA [11, 12]. However, other abnormalities such as increased lymphocytic apoptosis, cytokine network, signaling pathway by costimulatory molecules and also the presence of predisposing major histocompatibility complex (MHC) alleles might be involved in the pathogenesis of SIgAD [13-15]. …”

Section: Introductionmentioning

confidence: 99%

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The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

Bagheri¹,

Sanaei²,

Yazdani³

et al. 2019

Int Arch Allergy Immunol

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Selective immunoglobulin A deficiency (SIgAD) is the most prevalent type of primary immunodeficiency disorder. The phenotypic feature of SIgAD is related to a defect in B lymphocyte differentiation into plasma cell-producing immunoglobulin A (IgA). In this review, we summarize the recent advances in this regard. Genetic (including major histocompatibility complex [MHC] and non-MHC genes), immunologic (including B and T lymphocyte subsets abnormality), cytokines/chemokines and their related receptors, apoptosis and microbiota defects are reviewed. The mechanisms leading to SIgAD are most likely multifactorial and it can be speculated that several pathways controlling B cells functions or regulating epigenetic of the IGHA gene encoding constant region of IgA heavy chain and long-term survival of IgA switched memory B cells and plasma cells may be defective in different SIgAD patients.

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Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency

et al. 2020

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Objective. Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency in Western countries. Patients can suffer from recurrent infections and autoimmune diseases because of a largely unknown aetiology. To increase insights into the pathophysiology of the disease, we studied memory B and T cells and cytokine concentrations in peripheral blood. Methods. We analysed 30 sIgAD patients (12 children, 18 adults) through detailed phenotyping of peripheral B-cell, CD8 + T-cell and CD4 + Tcell subsets, sequence analysis of IGA and IGG transcripts, in vitro B-cell activation and blood cytokine measurements. Results. All patients had significantly decreased numbers of T-cell-dependent (TD; CD27 + ) and T-cell-independent (TI; CD27 À ) IgA memory B cells and increased CD21 low B-cell numbers. IgM + IgD À memory B cells were decreased in children and normal in adult patients. IGA and IGG transcripts contained normal SHM levels. In sIgAD children, IGA transcripts more frequently used IGA2 than controls (58.5% vs. 25.1%), but not in adult patients. B-cell activation after in vitro stimulation was normal. However, adult sIgAD patients exhibited increased blood levels of TGF-b1, BAFF and APRIL, whereas they had decreased Th1 and Th17 cell numbers. Conclusion. Impaired IgA memory formation in sIgAD patients is not due to a B-cell activation defect. Instead, decreased Th1 and Th17 cell numbers and high blood levels of BAFF, APRIL and TGF-b1 might reflect disturbed regulation of IgA responses in vivo.These insights into B-cell extrinsic immune defects suggest the need for a broader ª immunological focus on genomics and functional analyses to unravel the pathogenesis of sIgAD.

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Monogenic mutations associated with IgA deficiency

Cited by 30 publications

References 95 publications

The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency

The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency

The Heterogeneous Pathogenesis of Selective Immunoglobulin A Deficiency

Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency

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