Primary association of a MICA allele with protection against rheumatoid arthritis

To determine whether major histocompatibility complex class I chain-related gene A (MICA) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) independently of the HLA-DRB1 shared epitope (SE).

Fifty-four Spanish families with an affected son or daughter and 211 consecutive RA patients were genotyped for HLA-DRB1, tumor necrosis factor a/b microsatellite alleles, and MICA transmembrane polymorphism. We performed a case-control comparison with the consecutive patients and an independent transmission disequilibrium test with the families.

The frequency of the MICA 6.0 allele was significantly reduced, compared with controls, in the group of SE+ patients (odds ratio 0.39, P = 0.0005). Additionally, the haplotypes containing this allele were preferentially not transmitted to the affected offspring (9 transmitted of 33; P = 0.007), independent of the presence or absence of an SE either in the same haplotype or in the other haplotype in the progenitor.

These data suggest that the MICA 6.0 allele is an independent marker of protection against RA in the SE+ group of RA patients.