title: Anti-TNF treatment blocks the induction of T cell-dependent humoral responses.
abstract: Experimental and human data suggest that tumour necrosis factor (TNF) blockade may affect B cell responses, in particular the induction of T cell-dependent (TD) humoral immunity. This study aimed to assess this hypothesis directly in patients with arthritis by analysing longitudinally the effect of TNF blockade on B cell activation and the maturation of humoral responses against TD and T cell-independent vaccines.
  
  
  
  Peripheral blood samples were obtained from 56 spondyloarthritis patients before and after treatment with either non-steroidal anti-inflammatory drug (NSAID) alone or TNF blockers and analysed for B cell activation, plasma cell differentiation, germinal centre versus extra-follicular B cell maturation, and somatic hypermutation. Vaccine responses to hepatitis B and Streptococcus pneumoniae were measured by ELISA.
  
  
  
  TNF blockade augmented B cell activation as reflected by the expression of early activation markers, CD40, and costimulatory molecules, without affecting differentiation towards plasmablasts. This was associated with a specific increase of the unswitched fraction of circulating memory B cells and a decreased level of somatic hypermutation in anti-TNF treated patients, indicating an impairment of the germinal centre-dependent B cell maturation. In agreement with these findings, TNF blockade profoundly suppressed the response to the TD vaccination against hepatitis B, whereas the T cell-independent response against pneumococcal polysaccharides was only modestly affected.
  
  
  
  These data indicate that TNF blockade severely impedes the induction of primary TD humoral responses, probably by interfering with the germinal centre reaction.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gabriela Franco
authors.initials: GF
authors.lastname: Salinas
authors.forename: Leen
authors.initials: L
authors.lastname: De Rycke
authors.forename: Barbara
authors.initials: B
authors.lastname: Barendregt
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Paramarta
authors.forename: Hulda
authors.initials: H
authors.lastname: Hreggvidsdottir
authors.forename: Tineke
authors.initials: T
authors.lastname: Cantaert
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects*; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D025242:Spondylarthropathies / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept