title: The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab.
abstract: OBJECTIVE
  Yearly vaccination against influenza is currently recommended to patients with rheumatoid Arthritis (RA). Antibody and cell-mediated responses are both involved in the defense against influenza. Humoral responses to influenza vaccine are impaired in RA patients treated with rituximab (RTX). The objectives of this study were to comparatively assess cell mediated and humoral responses to influenza vaccination in RA patients with or without RTX-induced CD20 B-cell depletion.
  
  
  METHODS
  Trivalent influenza subunit vaccine was administered to 46 RA patients and to 16 healthy controls. The RA group included 29 patients treated by RTX and 17 on conventional disease-modifying anti-rheumatic drugs (DMARDs), mostly methotrexate. Peripheral blood mononuclear cells and sera were obtained immediately before and 4-6 weeks after vaccination. Cell-mediated response to influenza antigens was evaluated by flow cytometry for activated CD4 T-cells. Humoral response was evaluated by haemagglutination inhibition assay.
  
  
  RESULTS
  Cellular response: Cell-mediated responses were comparable in RTX-treated vs. DMARDs-treated patients. The recall postvaccination CD4+ cellular response was similar in RA patients and healthy controls. A positive correlation was found between CD19+ cell count on the day of vaccination and cellular response in RTX-treated RA patients. Humoral response: The antibody response rate was significantly impaired in the RTX group: being 26.4%, 68.4% and 47.1% in RTX-treated, DMARDs-treated and controls, respectively.
  
  
  CONCLUSIONS
  Cellular immunity to influenza vaccination in RTX-treated patients was similar to DMARDs-treated patients and healthy controls, while humoral immunity was severely impaired. The preservation of cellular immunity may explain the relatively low rate of infection among B-cell depleted patients.
authors.affiliation: Department of Rheumatology, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, Tel Aviv 64239, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Arad
authors.forename: S
authors.initials: S
authors.lastname: Tzadok
authors.forename: S
authors.initials: S
authors.lastname: Amir
authors.forename: M
authors.initials: M
authors.lastname: Mandelboim
authors.forename: E
authors.initials: E
authors.lastname: Mendelson
authors.forename: I
authors.initials: I
authors.lastname: Wigler
authors.forename: H
authors.initials: H
authors.lastname: Sarbagil-Maman
authors.forename: D
authors.initials: D
authors.lastname: Paran
authors.forename: D
authors.initials: D
authors.lastname: Caspi
authors.forename: O
authors.initials: O
authors.lastname: Elkayam
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D018501:Antirheumatic Agents; D007252:Influenza Vaccines; D000069283:Rituximab; D008727:Methotrexate