title: Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor.
abstract: BACKGROUND
  As a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy.
  
  
  METHODS
  Peripheral blood samples were obtained from RA patients, including a subset treated with anti-TNF, and from healthy controls to examine influenza-specific responses following seasonal influenza vaccination. Serum antibody was measured by hemagglutination inhibition assay. The frequency of influenza vaccine-specific antibody secreting cells and memory B cells was measured by EliSpot. Plasmablast (CD19+IgD-CD27hiCD38hi) induction was measured by flow cytometry.
  
  
  RESULTS
  Compared with healthy controls, RA patients treated with anti-TNF exhibited significantly decreased influenza-specific serum antibody and memory B cell responses throughout multiple years of the study. The short-term influenza-specific effector B cell response was also significantly decreased in RA patients treated with anti-TNF as compared with healthy controls, and correlated with decreased influenza-specific memory B cells and serum antibody present at one month following vaccination.
  
  
  CONCLUSIONS
  RA patients treated with anti-TNF exhibit a compromised immune response to influenza vaccine, consisting of impaired effector and consequently memory B cell and antibody responses. The results suggest that the increased incidence and severity of infection observed in this patient population could be a consequence of diminished antigen-responsiveness. Therefore, this patient population would likely benefit from repeat vaccination and from vaccines with enhanced immunogenicity.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kobie
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.forename: Peter
authors.initials: P
authors.lastname: Bryk
authors.forename: Michael
authors.initials: M
authors.lastname: Barnes
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Ritchlin
authors.forename: Darren A
authors.initials: DA
authors.lastname: Tabechian
authors.forename: Allen P
authors.initials: AP
authors.lastname: Anandarajah
authors.forename: R John
authors.initials: RJ
authors.lastname: Looney
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Thiele
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Anolik
authors.forename: Andreea
authors.initials: A
authors.lastname: Coca
authors.forename: Chungwen
authors.initials: C
authors.lastname: Wei
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Rosenberg
authors.forename: Changyong
authors.initials: C
authors.lastname: Feng
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.forename: F Eun-Hyung
authors.initials: FE
authors.lastname: Lee
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sanz
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007156:Immunologic Memory / Q000276:immunology; D000069285:Infliximab; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate