Aspartic acid70 in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans
Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. I...
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Published in | Journal of translational autoimmunity (Online) Vol. 3; p. 100057 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier B.V
01.01.2020
Elsevier |
Subjects | |
Online Access | Get full text |
ISSN | 2589-9090 2589-9090 |
DOI | 10.1016/j.jtauto.2020.100057 |
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Summary: | Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers.
High-resolution HLA class II typing was performed using a sequence-based method.
The allele frequency of HLA-DRB1∗04:04 and -DRB1∗03:01 were significantly increased in patients with AITD and RA compared to healthy individuals, pC = 0.021, OR = 2.4, 95%CI = 1.19–4.75 and pC = 0.009, OR = 3.4, 95%CI = 1.42–7.93, respectively. Remarkably, these patients have a combined risk given by susceptibility HLA-DRB1 alleles that contain the shared epitope, pC = 0.03, OR = 1.7, IC95% = 1.07–2.76, and a lack of protective alleles carrying aspartic acid70, pC = 0.009, OR = 0.5, IC95% = 0.32–0.84.
The results suggest that patients with AITD and RA have an immunogenetic mechanism that combines the susceptibility alleles associated with both diseases. Importantly, it seems to be linked mainly to the lack of protective alleles with aspartic acid in the position 70, along with the presence of susceptibility alleles that have the sequences QRRAA, QKRAA, and RRRAA at positions 70–74.
Patients with AITD and RA have a characteristic immunogenetic signature, which could be useful for determining multiple autoimmunities and assessing their relatives’ risk of developing it.
•The HLA-DRB1∗04:04 and -DRB1∗03:01 are the susceptibility alleles in RA and AITD.•The susceptibility in RA and AITD involves HLA-DRB1 shared epitope alleles.•The Mexican mestizo admixture patterns explain the variety of SE alleles in RA and AITD.•The immunopathogenic mechanism involves lack of DRB1 alleles with aspartic acid at 70 position. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 2589-9090 2589-9090 |
DOI: | 10.1016/j.jtauto.2020.100057 |