Because the opsonophagocytic activity (OPA) is a measurement of antibody function, these results suggest that while the GMC response rate is lower in patients receiving ABT/MTX combination therapy, the antibodies that are produced in response to PPSV23 vaccination by this group are similarly functional. == Table 3. after vaccination, we measured the patients concentrations of antibodies against pneumococcal serotypes 6B and 23F using an enzyme-linked immunosorbent assay and determined their antibody functionality using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI). == Results == The pneumococcal serotype-specific IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the ABT group, the IgG responses for the 6B serotype were lower compared with those in the MTX alone or control groups, whereas the OI responses were similar to those in the other two groups. In a subgroup analysis, the pneumococcal serotype-specific IgG responses were significantly lower in both serotypes (6B and 23F) in the ABT/MTX group; however, the OI responses in the ABT group were not different from the control group. There was no association between the pneumococcal serotype-specific IgG and OI responses for the 6B serotype in patients receiving ABT in contrast to the control or MTX alone patients. No severe adverse effects were observed in any of the treatment groups. == Conclusions == OI responses indicate antibody functionality rather than simply their amount, so the similarity of these measurements between all three groups suggests that RA patients receiving ABT still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. The results suggest an influence of ABT Rabbit polyclonal to DDX3 on the humoral response to PPSV23 vaccination under MTX treatment; however, preserved opsonin responses are expected in RA patients treated with ABT plus MTX. == Trial registration == University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012. Keywords:Abatacept, Methotrexate, Opsonization index, Rheumatoid arthritis, 23-valent pneumococcal polysaccharide == Introduction == Patients with autoimmune rheumatic diseases are more susceptible to infectious complications during the course of their diseases. Rheumatoid arthritis (RA) treatment can induce immunosuppression and increase the risk of infection [1]. The introduction of biologics has been a major achievement in treating these diseases, but an increased risk of infection associated with these therapies has become evident [2]. Some infections can be prevented by vaccination, which if used appropriately will decrease the burden of infection [3]. It is important to determine if RA patients receiving biologics have normal responses to vaccines. Abatacept (ABT) selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation [4]. The efficacy of ABT has previously been demonstrated both in RA patients with an inadequate response to methotrexate (MTX) and in RA patients with an inadequate response to anti-tumor necrosis factor (TNF) therapy [5], and ABT has been approved for the treatment of RA in a number of countries, including Japan. The impact of ABT on humoral responses to T-cell-dependent antigens, such as bacteriophage X174 and keyhole limpet hemocyanin, was previously evaluated in patients treated with ABT, and the responses to these antigens were reduced [6]. Polysaccharides are able to elicit immune responses in the absence of T-cell help, although the magnitude of the response can be marginally affected by immunosuppressive treatments [7]. Recent studies with pneumococcal polysaccharide vaccines with a limited number of RA patients were performed, without control groups, suggesting an adequate response [8]. Regarding the pneumococcal vaccine, the polysaccharide and less T cell-dependent nature of the antigen [9], may account for the preserved immune response during costimulatory modulation with ABT. The results from the earlier report would be strengthened by an inclusion of the relevant control groups because it Mcl1-IN-1 is crucial to have a group of age-matched RA patients under treatment with MTX alone for comparison [10]. The objective of this study was to investigate the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in patients with established RA who were being treated with ABT alone or in combination with MTX. == Methods == == Study design and patient population == This immunogenicity study was nested within a randomized, Mcl1-IN-1 double-blind, controlled trial designed Mcl1-IN-1 to evaluate the effectiveness of the PPSV23 in reducing the incidence of pneumonia as a primary endpoint. Patients with clinically diagnosed RA were recruited in Japanese National Hospital Organization (NHO) hospitals across Japan (n = 32) from September 2010 to December 2012 [11]. A total of 932 RA patients were enrolled and randomized 1:1 to receive either the PPSV23 or placebo. Of these, paired serum samples were obtained before and after vaccination from 703 patients, 353 of which received PPSV23. Among these 353 patients,121 patients receiving disease-modifying anti-rheumatic drugs (DMARDs), MTX, or ABT with/without MTX were subjected to the nested study for vaccine immunogenicity (Fig.1). == Fig. 1. == Flow diagram of patient recruitment Eligible patients were also found to be at risk for developing respiratory infections. RA patients were divided into the following groups: (1) patients with rheumatoid lung disease, (2) patients with RA treated with biological realtors, and (3) sufferers treated with immunosuppressive realtors..