HLA antigens and haplotypes in IgA‐deficient Brazilian paediatric patients

Gerbase‐DeLima, Maria; Pinto, Luiz Carlos; Grumach, Anete Sevciovic; Carneiro‐Sampaio, Magda

doi:10.1046/j.1365-2370.1998.00098.x

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…The absence of secretory IgA in the mucosal surfaces compromises mucosal integrity, thus allowing for unhindered passage of environmental antigens into the systemic circulation, and these dietary proteins may result in cross-reactions with self-antigens. Antibodies against cow's milk, among other autoantibodies, have Besides the above-mentioned immune mechanisms, it has been postulated that homozygosity for certain haplotypes of the major histocompatibility complex genes could be a risk factor for the development of some autoimmune diseases in patients with sIgAD, with some studies showing a higher frequency of certain MHC haplotypes in individuals with sIgAD and their families (36,37). Recently, the possibility of a link between some non-HLA candidate genes and sIgAD has been reported (38).…”

Section: Discussionmentioning

confidence: 99%

“…Besides the above-mentioned immune mechanisms, it has been postulated that homozygosity for certain haplotypes of the major histocompatibility complex genes could be a risk factor for the development of some autoimmune diseases in patients with sIgAD, with some studies showing a higher frequency of certain MHC haplotypes in individuals with sIgAD and their families (36,37). Recently, the possibility of a link between some non-HLA candidate genes and sIgAD has been reported (38).…”

Section: Discussionmentioning

confidence: 99%

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Allergic and autoimmune disorders in families with selective IgA deficiency

et al. 2017

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Background/aim: IgA deficiency is the most common human primary immunodeficiency. The prevalence of allergic disorders and autoimmunity is thought to be increased in selective IgA deficiency (sIgAD). However, it is currently unclear if these disorders coincide within these families. We aimed to evaluate the frequency of allergic and autoimmune disorders in children with sIgAD and their firstdegree relatives (FDRs). Materials and methods:The study included 81 children diagnosed with sIgAD and 274 of their FDRs. The presence of allergic and autoimmune disorders was evaluated and serum antithyroglobulin and antithyroid peroxidase levels were measured in both patients and their first-degree relatives. Results:The mean age of the patients was 9.9 ± 3.9 years. Among the patients with sIgAD, 45.7% of them had at least one allergic disorder and 17.3% of them had at least one autoimmune disorder. The frequencies of asthma, allergic rhinitis, and eczema in the FDRs of sIgAD patients were 10.9%, 9.1%, and 7.7%, respectively. Among their FDRs, 14.6% had autoimmunity, compared to an estimate of 5% in the general population. Conclusion:Increased frequency of allergic and autoimmune disorders in patients with sIgAD and their FDRs suggests a possible common predisposing genetic component for sIgAD and autoimmunity in these families.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Allergic and autoimmune disorders in families with selective IgA deficiency

et al. 2017

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“…6,7 No primary genetic factor has been identified and variation in familial inheritance patterns suggests that IgAD may be due to multiple genetic defects. Several studies have shown association of HLA alleles with IgAD, [8][9][10][11] and the extended haplotype HLA-A1-B8-DR3 occurs more frequently in individuals with IgAD than it does in the general population. This haplotype is known as an autoimmunity risk haplotype as it is associated with several autoimmune pathologies.…”

Section: Introductionmentioning

confidence: 99%

The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency

et al. 2008

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IgA deficiency (IgAD) and common variable immunodeficiency (CVID) often co-occur in families, associating with chronic inflammatory diseases such as celiac disease (CD). ICOS (inducible co-stimulator) and CTLA4 (cytotoxic T-lymphocyteassociated protein-4) may be important in both disorders, as ICOS is necessary for Ig class-switching and CTLA4 negatively regulates T-cell activation. Linkage and association of CD with CTLA4-ICOS is well documented, we thus aimed to further pinpoint CD susceptibility by haplotype-tagging analysis. We genotyped 663 CD families from Finland and Hungary, 575 additional CD patients from Finland, Hungary and Italy; 275 Swedish and Finnish IgAD individuals and 87 CVID individuals for 14-18 genetic markers in CTLA4-ICOS. Association was found between CTLA4-ICOS and both IgAD (P ¼ 0.0015) and CVID (P ¼ 0.0064). We confirmed linkage of CTLA4-ICOS with CD (LOD 2.38, P ¼ 0.0005) and found association of CTLA4-ICOS with CD (P ¼ 0.0009). Meta-analysis of the IgAD, CVID and CD materials revealed intergenic association (P ¼ 0.0005). Disease-associated markers were associated with lower ICOS and higher CTLA4 expression, indicating that the risk haplotypes contain functional variants. In summary, we identified a novel shared risk locus for IgAD, CVID and CD, the first report of association between CTLA4-ICOS and IgAD. Association between CD and CTLA4-ICOS was also confirmed in a large European data set.

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“…For example, as described above, the HLA 8.1 haplotype is commonly related to different autoimmune diseases (i.e. type 1 diabetes and rheumatoid arthritis) and SIgAD ( 112 – 116 , 131 , 132 ). Also, both SIgAD and autoimmune disorders show familial clustering ( 58 , 131 , 133 ) and therefore, the increased frequency in autoimmune disorders might suggest a possible common genetic component in SIgAD and autoimmunity.…”

Section: Different Clinical Manifestations Of Sigadmentioning

confidence: 99%

Innate Mechanisms in Selective IgA Deficiency

Zhang

Oostrom

et al. 2021

Front. Immunol.

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Selective IgA deficiency (SIgAD), characterized by a serum IgA level below 0.07 mg/ml, while displaying normal serum levels of IgM and IgG antibodies, is the most frequently occurring primary immunodeficiency that reveals itself after the first four years after birth. These individuals with SIgAD are for the majority healthy and even when they are identified they are usually not investigated further or followed up. However, recent studies show that newborns and young infants already display clinical manifestations of this condition due to aberrancies in their immune defense. Interestingly, there is a huge heterogeneity in the clinical symptoms of the affected individuals. More than 50% of the affected individuals do not have clinical symptoms, while the individuals that do show clinical symptoms can suffer from mild to severe infections, allergies and autoimmune diseases. However, the reason for this heterogeneity in the manifestation of clinical symptoms of the individuals with SIgAD is unknown. Therefore, this review focusses on the characteristics of innate immune system driving T-cell independent IgA production and providing a mechanism underlying the development of SIgAD. Thereby, we focus on some important genes, including TNFRSF13B (encoding TACI), associated with SIgAD and the involvement of epigenetics, which will cover the methylation degree of TNFRSF13B, and environmental factors, including the gut microbiota, in the development of SIgAD. Currently, no specific treatment for SIgAD exists and novel therapeutic strategies could be developed based on the discussed information.

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HLA antigens and haplotypes in IgA‐deficient Brazilian paediatric patients

Cited by 10 publications

References 26 publications

Allergic and autoimmune disorders in families with selective IgA deficiency

Allergic and autoimmune disorders in families with selective IgA deficiency

The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency

Innate Mechanisms in Selective IgA Deficiency

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