title: Pneumococcal polysaccharide vaccination in rheumatoid arthritis patients receiving tacrolimus.
abstract: BACKGROUND
  In rheumatoid arthritis (RA) patients receiving immunosuppressive treatments, vaccination against Streptococcus pneumoniae is recommended. The objective of the study was to evaluate the effects of tacrolimus (TAC) on immune response following administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) in patients with established RA.
  
  
  METHODS
  Patients with RA (n = 133) were vaccinated with PPSV23. Patients were classified into TAC (n = 29), methotrexate (MTX) (n = 55), control (n = 35), and TAC/MTX (n = 14) treatment groups. We measured the concentrations of pneumococcal serotypes 6B and 23F by using an enzyme-linked immunosorbent assay and determined antibody functionality by using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI), before and 4 to 6 weeks after vaccination. A positive antibody response was defined as at least a twofold increase in the IgG concentration or as at least a 10-fold increase in the OI.
  
  
  RESULTS
  IgG concentrations and OIs were significantly increased in all treatment groups after PPSV23 vaccination. The TAC treatment group appears to respond in a manner similar to that of the RA control group in terms of 6B and 23F serotype concentration and function. In contrast, the MTX group had the lowest immune response. Patients who received a combination of TAC and MTX (TAC/MTX) also had a diminished immune response compared with those who received TAC alone.
  
  
  CONCLUSIONS
  TAC monotherapy does not appear to impair PPSV23 immunogenicity in patients with RA, whereas antibody production and function may be reduced when TAC is used with MTX. Thus, PPSV23 administration during ongoing TAC treatment should be encouraged for infection-prone TAC-treated patients with rheumatic diseases.
  
  
  BACKGROUND
  University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.
authors.affiliation: Japanese National Hospital Organization (NHO, EBM study group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan. migita@nagasaki-mc.com.|Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, 856-8652, Japan. migita@nagasaki-mc.com.
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authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-8563, Japan. akeda@biken.osaka-u.ac.jp.
authors.forename: Yukihiro
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authors.affiliation: Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose, Tokyo, 204-8588, Japan. makazawa@my-pharm.ac.jp.
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authors.affiliation: Japanese National Hospital Organization (NHO, EBM study group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan. s-touma@sagamihara-hosp.gr.jp.
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authors.affiliation: Japanese National Hospital Organization (NHO, EBM study group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan. hirano@asahikawa.hosp.go.jp.
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authors.affiliation: Japanese National Hospital Organization (NHO, EBM study group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan. ideguchi@cronos.ocn.ne.jp.
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authors.affiliation: Japanese National Hospital Organization (NHO, EBM study group), Higashigaoka 2-5-23, Meguro, Tokyo, 152-8621, Japan. ryu-ma@cehpnet.com.
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mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D016559:Tacrolimus; D008727:Methotrexate