High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

Clin Exp Immunol. 2013 Nov;174(2):212-20. doi: 10.1111/cei.12162.

Abstract

This study aimed to examine the frequency of different subsets of circulating B and T follicular helper (Tfh) cells in patients with new-onset rheumatoid arthritis (RA) and following standard therapies. Twenty-five RA patients and 15 healthy controls (HC) were recruited for characterizing the frequency of CD27⁺, immunoglobulin (Ig)D⁺, CD86⁺, CD95⁺, Toll-like receptor (TLR)-9⁺ B cells and inducible T cell co-stimulator (ICOS) and programmed death 1 (PD-1)-positive Tfh cells and the level of serum interleukin (IL)-21. The potential correlation between the frequency of different subsets of B and Tfh cells and the values of clinical measures in RA patients was analysed. In comparison with HC, significantly higher percentages of circulating IgD⁺ CD27⁻ CD19⁺ naive B, CD86⁺ CD19⁺ and CD95⁺ CD19⁺ activated B, CD3⁺ CD4⁺ CXCR5⁺, CD3⁺ CD4⁺ CXCR5⁺ ICOS⁺, CD3⁺ CD4⁺ CXCR5⁺ PD-1⁺ and CD3⁺ CD4⁺ CXCR5⁺ ICOS⁺ PD-1⁺ Tfh cells but lower IgD⁺ CD27⁺ CD19⁺ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL-21 in the RA patients. Furthermore, the percentages of CD95⁺ B cells were correlated positively with the frequency of PD-1⁺ Tfh cells, but negatively with ICOS⁺ Tfh cells. The percentages of CD86⁺ B cells and ICOS⁺ Tfh cells were correlated positively with the values of disease activity score 28 (DAS28). Following the drug therapies for 1 month, the percentages of CD86⁺ B and PD-1⁺ Tfh cells were reduced significantly in the drug-responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers for evaluating the therapeutic responses of individual patients with RA.

Keywords: B cells; CD86; RA; Tfh cells; therapy.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocytes / immunology*
  • Biomarkers, Pharmacological / metabolism
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin D / metabolism
  • Immunologic Memory
  • Immunophenotyping
  • Inducible T-Cell Co-Stimulator Protein / metabolism*
  • Lymphocyte Activation
  • Lymphocyte Subsets / immunology*
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Toll-Like Receptor 9 / metabolism

Substances

  • Antigens, CD
  • Biomarkers, Pharmacological
  • ICOS protein, human
  • Immunoglobulin D
  • Inducible T-Cell Co-Stimulator Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Toll-Like Receptor 9