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Regulatory B cells in ANCA-associated vasculitis
  1. B Wilde1,2,
  2. M Thewissen1,
  3. J Damoiseaux3,
  4. S Knippenberg1,
  5. M Hilhorst1,
  6. P van Paassen1,
  7. O Witzke2,
  8. J W Cohen Tervaert1
  1. 1Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands
  2. 2Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
  3. 3Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands
  1. Correspondence to Dr Jan Willem Cohen Tervaert, Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, PO Box 5800, Maastricht 6202 AZ, The Netherlands; jw.cohentervaert{at}maastrichtuniversity.nl

Abstract

Objectives B cells have immunoregulatory function acting as antigen-presenting cells. A separate subset of interleukin (IL)-10 producing B cells (Breg) regulating T cell mediated immunity has been identified. In the present study, we investigated the role of Breg in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV).

Methods 17 healthy controls (HCs) and 41 patients with AAV were enrolled. 30 patients with AAV were in remission. Furthermore, 11 patients with AAV with active disease were studied. Breg were defined as IL-10+CD19+ B cells upon culture with cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) 2006. Next to Breg, CD4+CD127lowCD25hiCD39neg/CD39+ regulatory T-cells (Treg), interferon (IFN)γ+, IL-4+ and Il-17A+T helper cell subsets were determined via flow cytometry.

Results Patients with active or quiescent disease showed a diminished fraction of Breg as compared with HCs. The frequency of IFNγ+ T helper cells was negatively associated with Breg in untreated AAV in remission but not in active vasculitis or in HCs. Interestingly, the total Treg population and the CD39+ Treg subpopulation correlated positively with Breg in inactive patients with AAV.

Conclusions IL-10 producing B cells are diminished in AAV. Furthermore, Breg might regulate Th1 cells and are associated with Treg in quiescent AAV. Suppression of Th1 cells by Breg may be insufficient in active AAV.

  • Systemic vasculitis
  • T Cells
  • B cells
  • Autoantibodies
  • Autoimmune Diseases

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