Circulating T follicular helper cell and regulatory T cell frequencies are influenced by B cell depletion in patients with granulomatosis with polyangiitis

Yuan Zhao, Pamela M. K. Lutalo, Jessica E. Thomas, Shirish Sangle, Lee Meng Choong, Jennifer R. Tyler, Timothy Tree, Jo Spencer*, David D’Cruz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Objective. Granulomatosis with polyangiitis (GPA) is a rare and sometimes fatal systemic autoimmune disease. ANCAs specific for PR3 are associated with GPA. Remission in GPA can be achieved through B cell depletion (BCD) therapy. Our aim was to understand whether the frequencies of T cell subsets are influenced by BCD.

Methods. The frequencies of circulating T follicular helper cells (cTFHs) and regulatory T cells (Tregs) from 36 GPA patients including 11 rituximab-treated patients and 10 healthy controls were studied by flow cytometry. The functional capacity of Tregs was assessed by in vitro co-culture assays.

Results. We observed an increased frequency of cTFHs and a reduced frequency of antigen-experienced Tregs in peripheral blood from GPA patients on conventional therapies but not in those treated with rituximab compared with healthy controls. Furthermore, the ratio of cTFHs to Tregs was significantly higher in GPA patients on conventional therapies than in GPA patients treated with rituximab who were clinically improved or controls. Whereas Tregs were numerically reduced in GPA patients on conventional therapy, the suppressive capacity of Tregs on a per cell basis was not significantly altered in these individuals.

Conclusion. Our study illustrated increased cTFHs with decreased antigen-experienced Tregs in GPA patients on conventional therapies, but in B cell-depleted patients the levels of cTFHs and Tregs were similar to healthy controls. The negative correlation between cTFHs and Tregs implies the balance between T cell subsets and its B cell dependence impact on disease activity in GPA.
Original languageEnglish
Pages (from-to)621-630
Number of pages10
JournalRheumatology
Volume53
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

  • granulomatosis with polyangiitis (GPA)
  • follicular helper T (TFH)
  • regulatory T (Treg) cells
  • B cell depletion
  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • ANCA-ASSOCIATED VASCULITIS
  • WEGENERS-GRANULOMATOSIS
  • RITUXIMAB
  • EXPRESSION
  • CYCLOPHOSPHAMIDE
  • AUTOIMMUNITY
  • PROTEINASE-3
  • SUPPRESSION
  • MATURATION

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