title: Induction of autoimmune valvular heart disease by recombinant streptococcal m protein.
abstract: Rheumatic heart disease is an autoimmune sequela of group A streptococcal infection. Previous studies have established that streptococcal M protein is structurally and immunologically similar to cardiac myosin, a well-known mediator of inflammatory heart disease. In this study, we investigated the hypothesis that streptococcal M protein could produce inflammatory valvular heart lesions similar to those seen in rheumatic fever (RF). Fifty percent (3 of 6) of Lewis rats immunized with recombinant type 6 streptococcal M protein (rM6) developed valvulitis as well as focal lesions of myocarditis. Valvular lesions initiated at the valve surface endothelium spread into the valve. Anitschkow cells and verruca-like lesions were present. T cells from rM6-immunized rats proliferated in the presence of purified cardiac myosin, but not skeletal myosin. A T-cell line produced from rM6-treated rats proliferated in the presence of cardiac myosin and rM6 protein. The study demonstrates that the Lewis rat is a model of valvular heart disease and that streptococcal M protein can induce an autoimmune cell-mediated immune attack on the heart valve in an animal model. The data support the hypothesis that a bacterial antigen can break immune tolerance in vivo, an important concept in autoimmunity.
authors.affiliation: Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Quinn
authors.forename: S
authors.initials: S
authors.lastname: Kosanke
authors.forename: V A
authors.initials: VA
authors.lastname: Fischetti
authors.forename: S M
authors.initials: SM
authors.lastname: Factor
authors.forename: M W
authors.initials: MW
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D006349:Heart Valve Diseases / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D008943:Mitral Valve / Q000473:pathology; D009205:Myocarditis / Q000276:immunology / Q000503:physiopathology; D009218:Myosins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D011994:Recombinant Proteins; C014689:streptococcal M protein; D009218:Myosins