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Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis

Todd, SK; Pepper, RJ; Draibe, J; Tanna, A; Pusey, CD; Mauri, C; Salama, AD; (2014) Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology , 53 (9) pp. 1693-1703. 10.1093/rheumatology/keu136. Green open access

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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.

Type: Article
Title: Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/keu136
Publisher version: http://dx.doi.org/10.1093/rheumatology/keu136
Language: English
Additional information: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Rheumatology following peer review. The version of record, Todd, SK; Pepper, RJ; Draibe, J; Tanna, A; Pusey, CD; Mauri, C; Salama, AD; (2014) Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology, 53 (9) pp. 1693-1703, is available online at: http://dx.doi.org/10.1093/rheumatology/keu136.
Keywords: ANCA-associated vasculitis, B lymphocyte subsets, B regulatory cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1427492
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