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: A Quinn, S Kosanke, V A Fischetti, S M Factor, M W Cunningham
• Journal: Infection and immunity (Infect Immun) Vol. 69 Issue 6 Pg. 4072-8 (Jun 2001) ISSN: 0019-9567 [Print] United States
• PMID: 11349078 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Bacterial Proteins
• Carrier Proteins
• Recombinant Proteins
• streptococcal M protein
• Myosins

Topics

• Animals
• Antigens, Bacterial
• Autoimmune Diseases (immunology, physiopathology)
• Bacterial Outer Membrane Proteins
• Bacterial Proteins (administration & dosage, genetics, immunology, pharmacology)
• Carrier Proteins (administration & dosage, genetics, immunology, pharmacology)
• Cell Line
• Disease Models, Animal
• Heart Valve Diseases (immunology, physiopathology)
• Humans
• Immunization
• Lymphocyte Activation
• Mitral Valve (pathology)
• Myocarditis (immunology, physiopathology)
• Myosins (pharmacology)
• Rats
• Rats, Inbred Lew
• Recombinant Proteins (administration & dosage, genetics, immunology)
• T-Lymphocytes (drug effects, immunology)