Reduced CD5(+) CD24(hi) CD38(hi) and interleukin-10(+) 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 (Bregs ), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+) CD24(hi) CD27(+) 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(hi) CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5(+) subset of CD24(hi) CD38(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.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA; UNC Kidney Center, University of North Carolina, Chapel Hill, NC, USA.
L T
LT
Aybar
J G
JG
McGregor
S L
SL
Hogan
Y
Y
Hu
C E
CE
Mendoza
E J
EJ
Brant
C J
CJ
Poulton
C D
CD
Henderson
R J
RJ
Falk
D O
DO
Bunch
D051997:ADP-ribosyl Cyclase 1 / Q000097:blood / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen / Q000097:blood / Q000276:immunology; D019013:CD40 Antigens / Q000097:blood / Q000276:immunology; D018956:CD5 Antigens / Q000097:blood / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012074:Remission Induction
D000276:Adjuvants, Immunologic; D019268:Antibodies, Antineutrophil Cytoplasmic; D051927:CD24 Antigen; C497889:CD24 protein, human; D019013:CD40 Antigens; D018956:CD5 Antigens; C408982:CPG-oligonucleotide; C508609:IL10 protein, human; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
AAV; ANCA; CD5; interleukin-10; regulatory B cells