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

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.

• Authors: Sarah Katrina Todd, Ruth J Pepper, Juliana Draibe, Anisha Tanna, Charles D Pusey, Claudia Mauri, Alan D Salama
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 53 Issue 9 Pg. 1693-703 (Sep 2014) ISSN: 1462-0332 [Electronic] England
• PMID: 24729396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunosuppressive Agents
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Rituximab

Topics

• Adult
• Aged
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy, immunology)
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• B-Lymphocyte Subsets (immunology)
• B-Lymphocytes, Regulatory (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)