Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients.

Objective: To determine whether major histocompatibility complex (MHC) polymorphisms are associated with a good or poor response to infliximab therapy in patients with rheumatoid arthritis (RA).
Methods: Seventy-eight infliximab-treated patients with RA were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, MHC class I chain-related gene A (MICA) transmembrane polymorphism alleles, and tumor necrosis factor a (TNFa), TNFb, TNFc, TNFd, TNFe, D6S273, HLA-B-associated transcript 2 (BAT2), and D6S2223 microsatellites. Chi-square tests were performed to compare allele proportions between responder and nonresponder patients. A control sample of 342 healthy individuals was also included to detect linkage disequilibrium between pairs of markers.
Results: Among responders, the frequency of the TNFa11;b4 minihaplotype was increased (41% versus 16% in nonresponders; P = 0.01) and that of the D6S273_3 allele was decreased (32% versus 56% in nonresponders; P = 0.04). The D6S273_4/BAT2_2 pair was much more frequently observed among responders (46% versus 11% in nonresponders; P = 0.001). When compared with controls, this pair of alleles was found to be associated only with the group of responder patients (46% in responders versus 17% in controls; P = 0.00002). Most of the time, these markers are present in a DRB1*0404/D6S273_4/BAT2_2/TNFa11;b4 context. No statistically significant differences were observed for MICA and D6S2223 polymorphisms and for shared epitope status.
Conclusion: The data suggest that genetic determinants of response to infliximab therapy exist in the HLA complex.