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.
Preview |
Text (Article)
Salama_Todd et al.pdf Download (774kB) | Preview |
Preview |
Text (Supplementary data)
Salama_Todd et al supplementary data.pdf Download (365kB) | Preview |
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 |
Archive Staff Only
 |
View Item |
