Background/Purpose:

Different alleles of MHC class II molecules have been associated either with risk to systemic sclerosis (SSc) or its subphenotypes. Due to the high cost of HLA typing, studies have been limited to small sample sizes, preventing definitive statements as to which HLA alleles are likely causal.

Methods:

We have imputed the MHC class I and II alleles of 2,296 cases and 5,356 controls from four countries with a method previously developed. Besides classical HLA alleles, we also imputed amino acid changes encoded by genetic variants within the different MHC molecules. We compared the frequencies of the different alleles between cases and controls for SNPs, amino acids and classical HLA alleles.

Results:

The accuracy of the imputations ranged from 84% to 94% depending on the alleles being imputed with an average of 92% for all alleles in both populations. We confirmed previous associations of HLA alleles with SSc or its auto-antibody positive subgroups (e.g. HLA-DRB1*0701, HLA-DPB1*1301, HLA-DRB1*1104, HLA-DQB1*0501). We define in deeper detail some of these associations down to the level of aminoacidic positions which affect epitope binding and relocate some previous SSc associations within auto-antibody positive subgroups. Furthermore, we describe new association of the HLA allele HLA-DRB1*0801 with the presence of anti-centromere auto-antibodies. 

Conclusion:

Our data indicate that most HLA associations are specific to the presence of auto-antibodies. Also, only MHC class II alleles are associated and not MHC class I.

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« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-major-histocompatibility-complex-class-ii-alleles-associated-with-systemic-sclerosis-through-imputation-strategy/