title: Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the influence of abatacept (ABA) and associated contributing factors on pandemic 2009 influenza A/H1N1 vaccine immunogenicity in rheumatoid arthritis (RA) patients.
  
  
  METHODS
  The response to a nonadjuvanted monovalent pandemic 2009 influenza A/H1N1 killed virus vaccine was analyzed in 11 RA patients using ABA (RA-ABA), most with concomitant nonbiologic disease-modifying antirheumatic drugs (DMARDS), and compared to 33 age-matched RA patients on methotrexate (MTX) and 55 healthy controls, all without previous seroprotection. Clinical and laboratory evaluations were performed before and 21 days after vaccination. Anti-influenza antibody titers were measured by hemagglutination inhibition assay. Seroprotection (antibody titers ≥1:40) and the factor increase (FI) in the geometric mean titers (GMTs) were calculated. Prevaccination lymphocyte counts and gammaglobulin levels were determined.
  
  
  RESULTS
  Sex distribution, disease duration, and the Disease Activity Score in 28 joints were similar in the RA groups (P > 0.05). After vaccination, seroprotection was significantly reduced in RA-ABA patients compared to RA-MTX patients (9% versus 58%; P = 0.006) and controls (69%; P ≤ 0.001). FI-GMT was severely reduced in RA-ABA patients compared to RA-MTX patients (1.8 [1.4-2.3] versus 8.7 [5.2-17.4]; P < 0.001) and controls (11.5 [8.0-16.7]; P ≤ 0.001). Lymphocyte counts were comparable in RA groups (P > 0.05), but RA-ABA patients had slightly lower gammaglobulin levels than RA-MTX patients (0.9 gm/dl [0.6-1.8] versus 1.2 gm/dl [0.8-1.7]; P = 0.03), although almost all were within the normal range values.
  
  
  CONCLUSIONS
  The current study established that ABA, in association with traditional DMARDs, significantly reduces the humoral response to pandemic 2009 influenza A/H1N1 vaccine in RA patients. The results suggest an influence of costimulatory modulation in humoral response to this vaccine.
authors.affiliation: Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. anademedeiros@yahoo.com
authors.forename: Ana C
authors.initials: AC
authors.lastname: Ribeiro
authors.forename: Ieda M
authors.initials: IM
authors.lastname: Laurindo
authors.forename: Lissiane K
authors.initials: LK
authors.lastname: Guedes
authors.forename: Carla G
authors.initials: CG
authors.lastname: Saad
authors.forename: Julio C
authors.initials: JC
authors.lastname: Moraes
authors.forename: Clóvis A
authors.initials: CA
authors.lastname: Silva
authors.forename: Eloisa
authors.initials: E
authors.lastname: Bonfa
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058873:Pandemics / Q000517:prevention & control; D011446:Prospective Studies
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D000069594:Abatacept