Immunization with a bacterial ATP-binding cassette transporter fragment suppresses autoimmunity and prolongs survival in MRL/lpr lupus-prone mice.
The present study was undertaken to better define the role of the U1 70 kDa antigen in a spontaneous murine model of systemic lupus erythematosus (SLE) by testing whether immunization with the U1 70 kDa polypeptide could alter the production of antibodies against U1 70 kDa or against other small nuclear ribonucleoproteins (snRNP), modify disease expression or alter survival. We found that, while immunization with a U1 70 kDa derived fusion protein (70 KFP) tended to delay the development of anti-snRNP antibodies in the sera of MRL/lpr mice, it had no effect on autoimmune-mediated renal disease or survival. Unexpectedly, it was found that MRL/lpr mice immunized with a 367 amino acid fragment of a bacterial ATP-binding cassette transporter, MFP, had prolonged survival compared to saline injection or U1 70 kDa immunization and that this was associated with a delay in the onset of SLE-like proliferative glomerulonephritis. This is the first study, to our knowledge, in which a bacterial ATP-binding cassette transporter was shown to be beneficial in treating a murine model of SLE. We report that MFP significantly prolonged longevity in the MRL/lpr murine model of SLE compared to saline injection or 70 KFP immunization and that improved survival was associated with a delay in the onset of SLE-like glomerulonephritis.
Chang
M
M
Medical Research Service, Harry S. Truman Memorial Veterans' Hospital, Division of Immunology and Rheumatology, Department of Internal Medicine, and Department of Pathology, University of Missouri, Columbia, MO 65212, USA.
Walker
S E
SE
Hoffman
R W
RW
D000419:Albuminuria; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007114:Immunization; D007668:Kidney / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D058619:Maltose-Binding Proteins; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000276:immunology*; D015996:Survival Rate; D013997:Time Factors
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001426:Bacterial Proteins; D002352:Carrier Proteins; D058619:Maltose-Binding Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human; C490687:Snrnp70 protein, mouse