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Induction of autoimmune valvular heart disease by recombinant streptococcal m protein
A Quinn1, S Kosanke, V A Fischetti
1Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
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.
Insights
Group A Streptococcus M protein can trigger autoimmune heart valve damage, mimicking rheumatic heart disease. This study shows streptococcal M protein induces valvulitis and myocarditis in a Lewis rat model, supporting autoimmunity concepts.
Area of Science:
- Immunology
- Cardiology
- Microbiology
Background:
- Rheumatic heart disease (RHD) is an autoimmune condition following group A streptococcal infections.
- Streptococcal M protein shares similarities with cardiac myosin, a known factor in heart inflammation.
- Previous research suggests a link between streptococcal M protein and inflammatory heart disease.
Purpose of the Study:
- To investigate if streptococcal M protein can induce inflammatory valvular heart lesions.
- To determine if streptococcal M protein can cause autoimmune responses against heart valves.
- To establish a Lewis rat model for studying valvular heart disease induced by streptococcal M protein.
Main Methods:
- Lewis rats were immunized with recombinant type 6 streptococcal M protein (rM6).
- Histopathological examination of heart tissues was performed to identify valvulitis and myocarditis.
- T-cell proliferation assays were conducted using cardiac myosin and streptococcal M protein.
Main Results:
- Fifty percent of immunized rats developed valvulitis and myocarditis.
- Valvular lesions originated at the endothelium and progressed into the valve, showing Anitschkow cells and verruca-like lesions.
- T cells from immunized rats proliferated in response to cardiac myosin and rM6 protein, but not skeletal myosin.
Conclusions:
- Streptococcal M protein can induce an autoimmune, cell-mediated attack on heart valves in an animal model.
- The Lewis rat serves as a viable model for studying valvular heart disease.
- The findings support the hypothesis that bacterial antigens can break immune tolerance in vivo, contributing to autoimmunity.