MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility R. Lopez-Arbesu, F. J. Ballina-Garcia 1 , M. Alperi-Lopez 1 ,A. Lopez-Soto, S. Rodriguez-Rodero 2 , J. Martinez-Borra 2 ,A. Lopez-Vazquez 2 , J. L. Fernandez-Morera 2 ,

Objectives. Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of B-like (IBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. Methods. A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism � 62 of the IBL gene. Results. A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, Pc ¼ 0.01, OR ¼ 2.1, 95% CI ¼ 1.3–3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, Pc ¼ 0.04, OR ¼ 3.2, 95% CI ¼ 1.3–8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P ¼ 0.02, Pc ¼ NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, Pc ¼ 0.01, OR ¼ 2.2, 95% CI ¼ 1.3–3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (s ¼ 0.33) and HLA-DRB1*0405 (s ¼ 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P ¼ 0.04). No significant association between IBL and MICA with RA was found. Conclusions. MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.