title: Circulating T follicular helper cell and regulatory T cell frequencies are influenced by B cell depletion in patients with granulomatosis with polyangiitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Peter Gorer Department of Immunobiology, 2nd floor Borough Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. jo.spencer@kcl.ac.uk.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Pamela M K
authors.initials: PM
authors.lastname: Lutalo
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Thomas
authors.forename: Shirish
authors.initials: S
authors.lastname: Sangle
authors.forename: Lee Meng
authors.initials: LM
authors.lastname: Choong
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Tyler
authors.forename: Timothy
authors.initials: T
authors.lastname: Tree
authors.forename: Jo
authors.initials: J
authors.lastname: Spencer
authors.forename: David P
authors.initials: DP
authors.lastname: D'Cruz
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D018920:Coculture Techniques; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab
keywords: B cell depletion; follicular helper T (TFH); granulomatosis with polyangiitis (GPA); regulatory T (Treg) cells