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

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  • Additional Information
    • Source:
      Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Print ISSN: 0022-1767 (Print) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: Bethesda, MD : American Association of Immunologists
      Original Publication: Baltimore : Williams & Wilkins, c1950-
    • Subject Terms:
      Immune Tolerance* ; Self Tolerance*/drug effects; Autoantibodies/*immunology ; Lupus Erythematosus, Systemic/*immunology ; Lupus Nephritis/*immunology; Animals ; Antibodies, Antiphospholipid/biosynthesis ; Apoptosis/immunology ; Autoantibodies/biosynthesis ; Autoantigens/immunology ; CD28 Antigens/immunology ; Disease Models, Animal ; Immunization ; Immunodominant Epitopes/immunology ; Immunoglobulin G/biosynthesis ; Immunoglobulin G/immunology ; Immunoglobulin M/biosynthesis ; Immunoglobulin M/immunology ; Lipopolysaccharides/immunology ; Lipopolysaccharides/pharmacology ; Lupus Erythematosus, Systemic/pathology ; Lupus Nephritis/pathology ; Mice ; Mice, Inbred Strains ; Tumor Necrosis Factor-alpha/pharmacology
    • 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 beta(2)-glycoprotein I, an apoptotic cell-binding protein, in the presence of LPS induces a long-lived, potent response to beta(2)-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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    • Grant Information:
      67101 Canada Canadian Institutes of Health Research; DK 59793 United States DK NIDDK NIH HHS; 42391 Canada Canadian Institutes of Health Research; HL 69722 United States HL NHLBI NIH HHS; R01 DK059793 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Indexing Agency: NLM Local ID #: CAMS2312.
    • Accession Number:
      0 (Antibodies, Antiphospholipid)
      0 (Autoantibodies)
      0 (Autoantigens)
      0 (CD28 Antigens)
      0 (Immunodominant Epitopes)
      0 (Immunoglobulin G)
      0 (Immunoglobulin M)
      0 (Lipopolysaccharides)
      0 (Tumor Necrosis Factor-alpha)
    • Publication Date:
      Date Created: 20061024 Date Completed: 20061213 Latest Revision: 20190516
    • Publication Date:
      20231215
    • Accession Number:
      PMC3439500
    • Accession Number:
      10.4049/jimmunol.177.9.6504
    • Accession Number:
      17056583