Cited by 51Systemic Lupus Erythematosus ResearchT-cell and B-cell ImmunologySystemic Sclerosis and Related Diseases

Immunization with an Apoptotic Cell-Binding Protein Recapitulates the Nephritis and Sequential Autoantibody Emergence of Systemic Lupus Erythematosus

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Levine, Jerrold S, Subang, Rebecca, Nasr, Samih H, Fournier, Sylvie, Lajoie, Ginette, Wither, Joan, Rauch, Joyce·2006·The Journal of Immunology

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.

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Authors
Levine, J. S., Subang, R., Nasr, S. H., Fournier, S., Lajoie, G., Wither, J., & Rauch, J.
Affiliations
  • University of Illinois Chicago (US)
  • McGill University Health Centre (CA)
  • Jewish General Hospital (CA)
  • McGill University (CA)
  • Mount Sinai Hospital (CA)
  • University Health Network (CA)
Venue
The Journal of Immunology
Published
2006-11-01
Volume
177
Issue
9
Pages
6504-6516
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2159031154
Cited by
51
References
37
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 2
FWCI
1.54
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • McGill University
  • National Institutes of Health (5r21hl069722-02)
  • Canadian Institutes of Health Research (67101, 42391)
  • National Heart, Lung, and Blood Institute (HL69722)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 59793, R01DK059793)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
Keywords
systemic lupus erythematosus, beta2-glycoprotein I, lupus nephritis, glomerulonephritis, loss of tolerance, T cell response, lipopolysaccharide, autoantigens, murine lupus model
MeSH terms
Animals, Autoantibodies, Autoantigens, Disease Models, Animal, Immunoglobulin G, Immunoglobulin M, Immune Tolerance, Immunization, Lipopolysaccharides, Lupus Erythematosus, Systemic, Lupus Nephritis, Mice, Inbred Strains, Tumor Necrosis Factor-alpha, Immunodominant Epitopes, Antibodies, Antiphospholipid, Apoptosis, Self Tolerance, CD28 Antigens, Mice

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