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Similar CD19 Dysregulation in Two Autoantibody-Associated Autoimmune Diseases Suggests a Shared Mechanism of B-Cell Tolerance Loss |
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| Authors: | DONNA A. CULTON MATILDA W. NICHOLAS DONNA O. BUNCH QUAN LI ZHEN THOMAS B. KEPLER MARY ANNE DOOLEY CHANDRA MOHAN PATRICK H. NACHMAN STEPHEN H. CLARKE |
| Affiliation: | (1) Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;(2) Division of Nephrology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;(3) Center for Immunology, Department of Internal Medicine—Rheumatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA;(4) Department of Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA;(5) Division of Rheumatology and Immunology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;(6) Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA;(7) Department of Microbiology and Immunology, CB#7290,804 MEJB, University of North Carolina, Chapel Hill, NC 27599, USA |
| 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 na?ve 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. |
| Keywords: | B lymphocytes systemic lupus erythematosus ANCA small-vessel vasculitis CD19 autoimmunity autoantibodies |
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