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Induction of Autoimmune Valvular Heart Disease by Recombinant Streptococcal M Protein
Open accessAbstract
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.
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Crossreactivity between T cells targeting bacterial pathogens and the β-MyHC isoform has been validated in rat models for rheumatic heart disease.
“This crossreactivity has been further validated in rat models for rheumatic heart disease, suggesting the potential interplay between T cells targeting bacterial pathogens and the β -MyHC isoform. 285,286”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [285]
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Research works printed but not linked: 29
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Brimberg, L., Benhar, I., Mascaro-Blanco, A., Alvarez, K., Lotan, D., Winter, C., Klein, J., Moses, A. E., Somnier, F. E., Leckman, J. F., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.56 · Cited by 202
Self-citationAutoimmune Myocarditis, Old Dogs and New Tricks.
Won, T., Song, E. J., Kalinoski, H. M., Moslehi, J. J., & Čiháková, D. (2024) · Circulation Research · doi:10.1161/circresaha.124.323816 · Cited by 51
Metadata
- Authors
- Quinn, A., Kosanke, S., Fischetti, V. A., Factor, S. M., & Cunningham, M. W.
- Affiliations
- <!--label omitted: 1-->Departments of Microbiology and Immunology1 and
- University of Oklahoma Health Sciences Center (US)
- Rockefeller University (US)
- Albert Einstein College of Medicine (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2001-06
- Volume
- 69
- Issue
- 6
- Pages
- 4072-4078
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC98471
- OpenAlex
- W2164920442
- Cited by
- 151
- References
- 0
- Citations by year
- 2026: 11 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 7
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R56HL056267, R01HL056267, R37HL035280, HL-56267, HL35280)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Streptococcal Infections and Treatments
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- rheumatic heart disease, rheumatic fever, streptococcal M protein, Streptococcus pyogenes, valvulitis, myocarditis, cardiac myosin, autoimmunity, immune tolerance breaking, T cell proliferation, Lewis rat model
- MeSH terms
- Animals, Antigens, Bacterial, Autoimmune Diseases, Bacterial Outer Membrane Proteins, Bacterial Proteins, Carrier Proteins, Cell Line, Disease Models, Animal, Heart Valve Diseases, Humans, Immunization, Lymphocyte Activation, Mitral Valve, Myocarditis, Myosins, Rats, Inbred Lew, Recombinant Proteins, T-Lymphocytes, Rats
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