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 H. Nachman, Stephen H. Clarke

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 2007

Fingerprint

Autoantibodies
Autoimmune Diseases
B-Lymphocytes
Systemic Lupus Erythematosus
Vasculitis
Small Nuclear Ribonucleoproteins
B-Lymphocyte Subsets
Autoantigens
Proteome
Antigens
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. / Culton, Donna A.; Nicholas, Matilda W.; Bunch, Donna O.; Zhen, Quan Li; Kepler, Thomas B.; Dooley, Mary Anne; Mohan, Chandra; Nachman, Patrick H.; Clarke, Stephen H.

In: Journal of Clinical Immunology, Vol. 27, No. 1, 01.2007, p. 53-68.

Research output: Contribution to journalArticle

Culton, Donna A. ; Nicholas, Matilda W. ; Bunch, Donna O. ; Zhen, Quan Li ; Kepler, Thomas B. ; Dooley, Mary Anne ; Mohan, Chandra ; Nachman, Patrick H. ; Clarke, Stephen H. / Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. In: Journal of Clinical Immunology. 2007 ; Vol. 27, No. 1. pp. 53-68.
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