title: Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss.
abstract: : We report here that dysregulation of CD19, a coreceptor that augments B-cell receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (SVV). The naïve B cells of nearly all SLE and ANCA-SVV patients express approximately 20% less CD19 than healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells. These CD19(hi) memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19(hi) SLE Pts exhibit a distinct autoantibody profile characterized by high levels of antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular autoantibodies. These findings have implications for autoreactive B-cell activation and suggest a shared mechanism of B-cell tolerance loss in these two diseases.
authors.affiliation: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Donna A
authors.initials: DA
authors.lastname: Culton
authors.forename: Matilda W
authors.initials: MW
authors.lastname: Nicholas
authors.forename: Donna O
authors.initials: DO
authors.lastname: Bunch
authors.forename: Quan Li
authors.initials: QL
authors.lastname: Zhen
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dooley
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Nachman
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Clarke
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods; D014657:Vasculitis / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D018941:Antigens, CD19; D001323:Autoantibodies