Projects per year
Abstract
OBJECTIVES
To determine a role for antineutrophil cytoplasmic antibody (ANCA)-activated neutrophils in promoting B cell survival through the release of B lymphocyte stimulator (BLyS).
METHODS
Neutrophil BLyS expression was measured by flow cytometry. Concentrations of BLyS in cell supernatants and donor serum samples were measured by ELISA. Cell survival assays were carried out using an L3055 cell line and viability measured by flow cytometry.
RESULTS
Tumour necrosis factor α and formyl-Met-Leu-Phe (fMLP) treatment of non-primed neutrophils and treatment of primed neutrophils with anti-PR3 ANCA IgG resulted in a significant increase in surface expression of BLyS within 30 min which returned to basal levels by 2 h. Supernatants from ANCA-stimulated neutrophils were shown to contain increased levels of BLyS and to promote the survival of the centroblast cell line L3055. Serum BLyS concentrations are increased in patients with active ANCA-associated systemic vasculitis and these levels are increased further following 1-3 months of treatment with rituximab.
CONCLUSIONS
ANCA specifically causes the release of BLyS from activated neutrophils which can support B cell survival in vitro. The presence of serum BLyS in active disease and its increase following B cell depletion suggest it is an important factor in disease pathogenesis and may facilitate disease relapse.
Original language | English |
---|---|
Pages (from-to) | 2229-33 |
Number of pages | 5 |
Journal | Annals of the Rheumatic Diseases |
Volume | 70 |
Issue number | 12 |
DOIs | |
Publication status | Published - 1 Dec 2011 |
Fingerprint
Dive into the research topics of 'ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process.'. Together they form a unique fingerprint.Projects
- 1 Finished
-
The role of neutrophil serine proteases in vasculitic glomerulonephritis and potential as therapeutic targets
Savage, C. (Principal Investigator), Rainger, E. (Co-Investigator) & Harper, L. (Co-Investigator)
1/06/07 → 30/11/11
Project: Research Councils