Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus

Jerrold S. Levine, Rebecca Subang, Samih H. Nasr, Sylvie Fournier, Ginette Lajoie, Joan Wither, Joyce Rauch

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The initial events predisposing to loss of tolerance in patients with systemic lupus erythematosus (SLE) are largely unknown, as are the events that precipitate the transition from preclinical to overt disease. We hypothesized that induction of murine SLE would require tipping the balance between tolerance and immunity in two ways: 1) an immunogen that could take advantage of apoptotic cells as a scaffold for epitope spread, and 2) an immune activator that would generate a strong and persistent T cell response to the inciting immunogen. We show that immunization of C57BL/6 and BALB/c mice with human β2-glycoprotein I, an apoptotic cell-binding protein, in the presence of LPS induces a long-lived, potent response to β2- glycoprotein I that results in epitope spread to multiple SLE autoantigens. SLE-specific autoantibodies emerged in a sequential manner that recapitulated the order seen in human SLE. Moreover, immunized mice developed overt glomerulonephritis closely resembling human lupus nephritis.

Original languageEnglish (US)
Pages (from-to)6504-6516
Number of pages13
JournalJournal of Immunology
Volume177
Issue number9
StatePublished - Nov 1 2006
Externally publishedYes

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Nephritis
Systemic Lupus Erythematosus
Autoantibodies
Immunization
Carrier Proteins
Epitopes
Glycoproteins
Lupus Nephritis
Autoantigens
Glomerulonephritis
Immunity
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Levine, J. S., Subang, R., Nasr, S. H., Fournier, S., Lajoie, G., Wither, J., & Rauch, J. (2006). Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus. Journal of Immunology, 177(9), 6504-6516.

Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus. / Levine, Jerrold S.; Subang, Rebecca; Nasr, Samih H.; Fournier, Sylvie; Lajoie, Ginette; Wither, Joan; Rauch, Joyce.

In: Journal of Immunology, Vol. 177, No. 9, 01.11.2006, p. 6504-6516.

Research output: Contribution to journalArticle

Levine, JS, Subang, R, Nasr, SH, Fournier, S, Lajoie, G, Wither, J & Rauch, J 2006, 'Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus', Journal of Immunology, vol. 177, no. 9, pp. 6504-6516.
Levine, Jerrold S. ; Subang, Rebecca ; Nasr, Samih H. ; Fournier, Sylvie ; Lajoie, Ginette ; Wither, Joan ; Rauch, Joyce. / Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus. In: Journal of Immunology. 2006 ; Vol. 177, No. 9. pp. 6504-6516.
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