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Anti-TNF treatment blocks the induction of T cell-dependent humoral responses
  1. Gabriela Franco Salinas1,
  2. Leen De Rycke1,2,
  3. Barbara Barendregt3,
  4. Jacqueline E Paramarta1,
  5. Hulda Hreggvidstdottir1,
  6. Tineke Cantaert1,4,
  7. Mirjam van der Burg3,
  8. Paul P Tak1,5,
  9. Dominique Baeten1
  1. 1Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  3. 3Department of Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands
  4. 4Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
  5. 5Glaxo Smith Kline, Stevenage, UK
  1. Correspondence to Dr Dominique Baeten, Clinical Immunology and Rheumatology, F4-105, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; d.l.baeten{at}


Objective 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.

Materials and methods 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.

Results 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.

Conclusions These data indicate that TNF blockade severely impedes the induction of primary TD humoral responses, probably by interfering with the germinal centre reaction.

  • B cells
  • Vaccination
  • Anti-TNF
  • Autoantibodies
  • T Cells

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