Immunoglobulin epitope spreading and autoimmune disease after peptide immunization: Sm B/B'-derived PPPGMRPP and PPPGIRGP induce spliceosome autoimmunity.
Autoantibodies from many patients with systemic lupus erythematosus bind the Sm autoantigen B/B' polypeptide. The binding of serial serum specimens to the 233 overlapping octapeptides of Sm B/B' have shown that of the B/B'-derived octapeptides, PPPGMRPP and PPPGIRGP are early targets of the autoimmune response in some lupus patients. Rabbits immunized with PPPGMRPP and PPPGIRGP develop antibodies which not only bind these octapeptides, but also subsequently bind many other octapeptides of Sm B/B'. Eventually, the rabbits immunized with one octapeptide develop autoantibodies that bind other spliceosomal proteins including D, 70K, A, and C. Any mechanisms that operate to maintain tolerance or anergy for the spliceosome are thus overcome. Features considered typical of human systemic lupus erythematosus are also found in these peptide-immunized animals, such as antinuclear antibodies, anti-Sm precipitins, anti-double-stranded DNA, thrombocytopenia, seizures, and proteinuria. This disease model provides access to a mechanism for the development of humoral autoimmunity and may provide a basis to explain the immunopathogenesis of lupus in humans.
James
J A
JA
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
Gross
T
T
Scofield
R H
RH
Harley
J B
JB
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007136:Immunoglobulins / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology*; D011817:Rabbits; D017411:Ribonucleoproteins, Small Nuclear; D017381:Spliceosomes / Q000276:immunology*; D055517:snRNP Core Proteins
D001324:Autoantigens; D000939:Epitopes; D007136:Immunoglobulins; D009842:Oligopeptides; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins