title: Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission.
abstract: OBJECTIVE
  Regulatory B cells (Bregs) constitute a subset of B cells with immunomodulatory properties. Numerical and functional alterations in the Breg compartment have been associated with autoimmunity. The aim of this study was to assess the frequency and function of Bregs in patients with ANCA-associated vasculitis (AAV).
  
  
  METHODS
  B cell subsets were determined in the peripheral blood of 48 AAV patients (12 active, 36 in remission) and 41 healthy controls (HCs) by flow cytometry. Bregs were defined within the CD19(+) population as CD24(hi)CD38(hi) or CD24(hi)CD27(+) cells. The percentage of IL-10-positive B cells in circulation was analysed by flow cytometry. Sorted CD19(+) B cells were co-cultured with monocytes to evaluate their capacity to inhibit monocyte TNF-α production upon lipopolysaccharide stimulation.
  
  
  RESULTS
  The frequency of circulating CD19(+)CD24(hi)CD38(hi) cells was not different in AAV patients in remission compared with HCs, but was decreased in patients with active disease [mean in HCs 5.5% (s.d. 1.6) vs active 3.8% (s.d. 2.8), P = 0.0104]. Furthermore, the percentage of CD19(+)CD24(hi)CD27(+) cells was significantly decreased in both remission and active patients when compared with HCs [HCs 15.0% (s.d. 9.3) vs remission 6.6% (s.d. 4.4) (P < 0.0001) vs active 6.4% (s.d. 6.2) (P = 0.0006)]. The frequency of IL-10-positive B cells was comparable between patients and HCs. B cells from AAV patients suppressed monocyte TNF-α production to a similar extent to cells from HCs.
  
  
  CONCLUSIONS
  Based on immunophenotypic classification, Bregs are numerically diminished in AAV patients. However, B cell function in terms of IL-10 production and their capacity to suppress monocyte activation is not compromised in AAV patients in remission.
authors.affiliation: Department of Pathology and Medical Biology, Department of Rheumatology and Clinical Immunology and Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nikola
authors.initials: N
authors.lastname: Lepse
authors.affiliation: Department of Pathology and Medical Biology, Department of Rheumatology and Clinical Immunology and Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.affiliation: Department of Pathology and Medical Biology, Department of Rheumatology and Clinical Immunology and Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Abraham
authors.initials: A
authors.lastname: Rutgers
authors.affiliation: Department of Pathology and Medical Biology, Department of Rheumatology and Clinical Immunology and Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.affiliation: Department of Pathology and Medical Biology, Department of Rheumatology and Clinical Immunology and Department 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, Department of Rheumatology and Clinical Immunology and Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. p.heeringa@umcg.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D016022:Case-Control Studies; D018920:Coculture Techniques; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003520:Cyclophosphamide; D011239:Prednisolone
keywords: ANCA-associated vasculitis; B cells; IL-10; regulatory B cells