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Publication Detail
Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Todd SK, Pepper RJ, Draibe J, Tanna A, Pusey CD, Mauri C, Salama AD
  • Publication date:
    09/2014
  • Pagination:
    1693, 1703
  • Journal:
    Rheumatology (Oxford)
  • Volume:
    53
  • Issue:
    9
  • Status:
    Published
  • Country:
    England
  • PII:
    keu136
  • Language:
    eng
  • Keywords:
    ANCA-associated vasculitis, B lymphocyte subsets, B regulatory cells, Adult, Aged, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Monoclonal, Murine-Derived, B-Lymphocyte Subsets, B-Lymphocytes, Regulatory, Case-Control Studies, Coculture Techniques, Female, Humans, Immune Tolerance, Immunophenotyping, Immunosuppressive Agents, Interleukin-10, Lymphocyte Activation, Male, Middle Aged, Remission Induction, Rituximab, Th1 Cells, Tumor Necrosis Factor-alpha
Abstract
OBJECTIVES: B cells are central to the pathology of ANCA-associated vasculitis (AAV), a disease characterized by autoantibodies and effectively treated by rituximab. In addition to promoting inflammation, a subset of B cells act to suppress harmful autoimmune responses (Breg). The balance of effector and regulatory B cell subsets in AAV is not known. This study was conducted to assess the relative frequency of these subsets during different states of disease activity. METHODS: B memory (Bmem), naive (Bnaive) and regulatory (Breg) subsets were defined by their relative expression of CD24 and CD38. Function was assessed by cytokine production and suppressive action on CD4(+) Th1 activation evaluated in a co-culture system. RESULTS: Compared with healthy controls, the frequency of Breg (CD24(hi)CD38(hi)) was significantly reduced during disease remission in both proteinase 3 (PR3)- and MPO-ANCA patients and during acute disease in PR3-ANCA patients, while the frequency of memory cells (CD24(hi)CD38(lo)) was reduced during active disease and restored during remission. Breg cell frequency showed a positive correlation, while Bmem had an inverse correlation with IL-10 production in vitro. B and T cell co-cultures revealed that memory and naive B cell subsets augmented Th1 activation in vitro, which was prevented by Breg, and this pattern did not differ between remission AAV patients and controls. CONCLUSION: In remission there is a numerical, but not functional, deficiency in Breg and preservation of Bmem associated with reduced IL-10 production and increased Th1 activation in vitro. This imbalance may contribute to the high rate of relapse observed in AAV, especially in PR3-ANCA patients.
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