Reduced CD5+CD24hiCD38hi and interleukin-10+ regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies

摘要

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 (Bregs), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19⁺CD24^hiCD38^hi and CD19⁺CD24^hiCD27⁺ Bregs were evaluated in addition to their CD5⁺ 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⁺CD24^hiCD38^hi B cells and IL-10⁺ B cells compared to patients in remission and healthy controls (HCs). As IL-10⁺ and CD5⁺CD24^hiCD38^hi B cells normalized in remission within an individual, ANCA titres decreased. The CD5⁺ subset of CD24^hiCD38^hi B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5⁺ B cells are enriched in the ability to produce IL-10 compared to CD5^neg B cells. Together these results suggest that CD5 may identify functional IL-10-producing Bregs. The malfunction of Bregs during active disease due to reduced IL-10 expression may thus permit ANCA production.