Reduced CD5 super(+)CD24 super(hi)CD3 8 super(hi) and interleukin-10 super(+) regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies

Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (B sub(regs)), play a role in immunologica...

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Published in:Clinical and experimental immunology 2015-05, Vol.180 (2), p.178-188
Main Authors: Aybar, L T, McGregor, J G, Hogan, S L, Hu, Y, Mendoza, CE, Brant, E J, Poulton, C J, Henderson, C D, Falk, R J, Bunch, DO
Format: Article
Language:English
Subjects:
Adeno-associated virus
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Summary:Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (B sub(regs)), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19 super(+)CD24 super(hi)CD 38 super(hi) and CD19 super(+)CD24 super(hi)CD 27 super(+) B sub(regs) were evaluated in addition to their CD5 super(+) subsets in 69 patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5 super(+)CD24 super(hi)CD3 8 super(hi) B cells and IL-10 super(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10 super(+) and CD5 super(+)CD24 super(hi)CD3 8 super(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5 super(+) subset of CD24 super(hi)CD38 super(hi) B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5 super(+) B cells are enriched in the ability to produce IL-10 compared to CD5 super(neg) B cells. Together these results suggest that CD5 may identify functional IL-10-producing B sub(regs). The malfunction of B sub(regs) during active disease due to reduced IL-10 expression may thus permit ANCA production.
ISSN:0009-9104
1365-2249
DOI:10.1111/cei.12483