Immunization with an Apoptotic Cell-Binding Protein Recapitulates the Nephritis and Sequential Autoantibody Emergence of Systemic Lupus Erythematosus
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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
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-11-01
- Volume
- 177
- Issue
- 9
- Pages
- 6504-6516
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3439500
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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