title: Regulatory and effector B cell cytokine production in patients with relapsing granulomatosis with polyangiitis.
abstract: BACKGROUND
  B cells are capable of producing regulatory and effector cytokines. In patients with granulomatosis with polyangiitis (GPA), skewing of the pro- and anti-inflammatory cytokine balance may affect the risk of relapse. This study aimed to investigate differences in B cell cytokine production in patients with relapsing GPA and in controls, and determine whether this can aid in relapse prediction.
  
  
  METHODS
  Thirteen GPA patients with an upcoming relapse were matched with non-relapsing patients and healthy controls in a retrospective design. The B cell subset distribution was determined from peripheral blood. Cryopreserved peripheral blood mononuclear cells were cultured and intracellular B cell production of regulatory (IL10) and effector (TNFα, IFNγ, IL2, IL6) cytokines was assessed. Finally, serum markers associated with B cell activation (sCD27) and migration (CCL19) were determined.
  
  
  RESULTS
  GPA patient samples exhibited significantly lower percentages of TNFα+ B cells than controls, an effect that was most pronounced in patients about to relapse. B cell capacity for IL10 production was similar in patients and controls. No significant differences were observed for cytokine production in relapsing and non-relapsing GPA patients. TNFα production correlated strongly with IL2, IFNγ and the percentage of memory B cells. No change in effector cytokines occurred before relapse, while the percentage of IL10+ B cells significantly decreased. GPA patients in remission had increased serum levels of CCL19 and sCD27, and sCD27 levels increased upon active disease.
  
  
  CONCLUSIONS
  While differences in effector B cell cytokine production were observed between patients and controls, monitoring this in GPA did not clearly distinguish patients about to relapse. Prospective measurements of the regulatory cytokine IL10 may have potential for relapse prediction. Memory B cells appear mainly responsible for effector cytokine production. Increased migration of these cells could explain the decreased presence of TNFα+ B cells in the circulation.
authors.affiliation: Department of Rheumatology and Clinical Immunology, AA21, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Land
authors.affiliation: Department of Rheumatology and Clinical Immunology, AA21, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan-Stephan F
authors.initials: JS
authors.lastname: Sanders
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.affiliation: Department of Rheumatology and Clinical Immunology, AA21, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. a.rutgers@umcg.nl.
authors.forename: Abraham
authors.initials: A
authors.lastname: Rutgers
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D016207:Cytokines
keywords: B-cells; CCL19; Cytokines; GPA; IL10; Relapse; TNFα; Vasculitis; sCD27