Reduced CD5+CD24hiCD38hi and interleukin-10+ regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies |
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Authors: | L T Aybar J G McGregor S L Hogan Y Hu C E Mendoza E J Brant C J Poulton C D Henderson R J Falk D O Bunch |
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Affiliation: | *Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA;†UNC Kidney Center, University of North Carolina, Chapel Hill, NC, USA |
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Abstract: | 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+CD24hiCD38hi and CD19+CD24hiCD27+ 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+CD24hiCD38hi B cells and IL-10+ B cells compared to patients in remission and healthy controls (HCs). As IL-10+ and CD5+CD24hiCD38hi B cells normalized in remission within an individual, ANCA titres decreased. The CD5+ subset of CD24hiCD38hi 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 CD5neg 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. |
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Keywords: | AAV ANCA CD5 interleukin-10 regulatory B cells |
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