Rheumatology Medical News about HLA class II, SSc, ACA, ATA, ARA, Fibrillarin

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Major Histocompatibility Complex (MHC) class II alleles, haplotypes, and epitopes which confer susceptibility or protection in the fibrosing autoimmune disease systemic sclerosis: Analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls
Annals of Rheumatic Diseases, 07/22/09

Arnett FC et al. - These data indicate unique and multiple HLA class II effects in systemic sclerosis (SSc), especially on autoantibody markers of different sub-phenotypes.

Methods

An association study to determine HLA-class II (DRB1, DQB1, DQA1, and DPB1) alleles, haplotypes and shared epitopes associated with SSc and its sub-phenotypes
1300 SSc cases (961 whites, 178 blacks and 161 Hispanics) characterized for:
- Clinical skin forms (limited vs diffuse)
- SSc- specific autoantibodies (anti-centromere (ACA)
- Anti-topoisomerase I (ATA)
- Anti-RNA polymerase III (ARA)
- Anti-U3 RNP (fibrillarin), and others
Statistical analyses in SSc itself by ethnicity, gender, skin type and autoantibodies were performed

Results

Strongest positive class II associations with SSc in whites and Hispanics were the DRB1*1104, DQA1*0501, DQB1*0301 haplotype, and DQB1 alleles encoding a non-leucine residue at position 26 (DQB1 26 epi)
While the DRB1*0701, DQA1*0201, DQB1*0202 haplotype and DRB1*1501 haplotype were negatively correlated and possibly protective in dominant and recessive models, respectively
These associations did not discriminate limited SSc from diffuse SSc
SSc in blacks was associated with DRB1*0804, DQA1*0501, DQB1*0301 alleles
DPB1*1301 showed the highest odds ratio for ATA
Moreover, it showed no LD or gene interaction with DR/DQ
ACA was best explainable by DQB1*0501 and DQB1*26 epi alleles and ARA by DRB1*0404, DRB1*11 and DQB1*03 alleles in whites and Hispanics but DRB1*08 in blacks

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