Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss

Donna A. Culton, Matilda W. Nicholas, Donna O. Bunch, Quan Li Zhen, Thomas B. Kepler, Mary Anne Dooley, Chandra Mohan, Patrick Nachman, Stephen H. Clarke

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 languageEnglish (US)
Pages (from-to)53-68
Number of pages16
JournalJournal of Clinical Immunology
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • ANCA small-vessel vasculitis
  • Autoantibodies
  • Autoimmunity
  • B lymphocytes
  • CD19
  • Systemic lupus erythematosus

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