Primary association of a MICA allele with protection against rheumatoid arthritis

Objective. To determine whether major histocompatibility complex class I ch ain-related gene A (MICA) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) independently of the HLA-DRB1 shared epitope ( SE). Methods. Fifty-four Spanish families with an affected son or daughter and 2 11 consecutive RA patients were genotyped for HLA-DRB1, tumor necrosis fact or a/b microsatellite alleles, and MICA transmembrane polymorphism. We perf ormed a case-control comparison with the consecutive patients and an indepe ndent transmission disequilibrium test with the families. Results. The frequency of the MICA 6.0 allele was significantly reduced, co mpared with controls, in the group of SE+ patients (odds ratio 0.39, P = 0. 0005). Additionally, the haplotypes containing this allele were preferentia lly not transmitted to the affected offspring (9 transmitted of 33; P = 0.0 07), independent of the presence or absence of an SE either in the same hap lotype or in the other haplotype in the progenitor. Conclusion. These data suggest that the MICA 6.0 allele is an independent m arker of protection against RA in the SE+ group of RA patients.