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Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis.
- 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.)
- Subjects :
- Adult
Aged
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis drug therapy
Antibodies, Monoclonal, Murine-Derived therapeutic use
B-Lymphocyte Subsets immunology
Case-Control Studies
Coculture Techniques
Female
Humans
Immune Tolerance immunology
Immunophenotyping
Immunosuppressive Agents therapeutic use
Interleukin-10 biosynthesis
Lymphocyte Activation immunology
Male
Middle Aged
Remission Induction
Rituximab
Th1 Cells immunology
Tumor Necrosis Factor-alpha biosynthesis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis immunology
B-Lymphocytes, Regulatory immunology
Subjects
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