Regulatory B cells in rheumatoid arthritis: Alterations in patients receiving anti-TNF therapy

Clin Immunol. 2017 Nov:184:63-69. doi: 10.1016/j.clim.2017.05.012. Epub 2017 May 12.

Abstract

Cytokines, including tumor necrosis factor alpha (TNFα) are involved in Rheumatoid arthritis (RA) pathogenesis by augmenting autoimmunity, sustaining long term inflammation in the synovium, and promoting joint damage. Anti-TNF therapy is one of the most efficient and widely used therapies for RA, although its mechanism is not clarified yet. Earlier we demonstrated that RA patients have a reduced number of IL-10 producing regulatory B cells (B10 cells) as compared to healthy individuals and they are functionally impaired. Our aim was to study the influence of anti-TNF therapy on B10 cells in RA, to follow the alteration of B cell activation markers (CD25, CD69) and to monitor the level of citrullinated peptid-specific antibodies and the secreted IL-10 in patients' sera during the therapy. We have observed that at six month after starting the therapy the frequency of B10 cells remarkably increased, while the expression of the activation marker, CD69 decreased on B cells. In contrast, serum levels of IL-10 and anti-citrullinated peptide antibodies did not change post-treatment.

Conclusion: The reduced activation state of B cells and the increasing number of regulatory B10. cells might contribute to the therapeutic efficacy of anti-TNF agents in RA.

Keywords: ACPA; Anti-TNF therapy; Il-10; Regulatory B cell; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adolescent
  • Adult
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology
  • B-Lymphocytes, Regulatory / immunology*
  • Drug Therapy, Combination
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Interleukin-10 / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lectins, C-Type / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antirheumatic Agents
  • Autoantibodies
  • CD69 antigen
  • IL10 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Peptides, Cyclic
  • Tumor Necrosis Factor-alpha
  • cyclic citrullinated peptide
  • Interleukin-10
  • Adalimumab
  • Etanercept
  • Methotrexate