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 ∼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 CD19hi memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19hi 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.
Original language | English (US) |
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Pages (from-to) | 53-68 |
Number of pages | 16 |
Journal | Journal of Clinical Immunology |
Volume | 27 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2007 |
Externally published | Yes |
Bibliographical note
Funding Information:We gratefully acknowledge the Flow Cytometry Facility at the University of North Carolina. We also extend our thanks to Sarah Thielman, Brenda Meier, Marcus R. Johnson, and Pamela Sullivan for their help in acquiring patient samples. This work was supported by National Institutes of Health Grants AI29576, AI43587 and DK58335. D. A. C. was supported by a Training Grant in Dermatological Research, T32 AR07369.
Keywords
- ANCA small-vessel vasculitis
- Autoantibodies
- Autoimmunity
- B lymphocytes
- CD19
- Systemic lupus erythematosus