Back to Search Start Over

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

Authors :
Todd SK
Pepper RJ
Draibe J
Tanna A
Pusey CD
Mauri C
Salama AD
Source :
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2014 Sep; Vol. 53 (9), pp. 1693-703. Date of Electronic Publication: 2014 Apr 11.
Publication Year :
2014

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.<br />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.<br />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.<br />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.<br /> (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1462-0332
Volume :
53
Issue :
9
Database :
MEDLINE
Journal :
Rheumatology (Oxford, England)
Publication Type :
Academic Journal
Accession number :
24729396
Full Text :
https://doi.org/10.1093/rheumatology/keu136