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.

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Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.

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