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.