Cytotoxic mAb from rheumatic carditis recognizes heart valves and laminin
Open accessAbstract
Anti-streptococcal antibodies cross-reactive with N-acetyl-betaD-glucosamine (GlcNAc) and myosin are present in the sera of patients with rheumatic fever (RF). However, their role in tissue injury is not clear. In this study, we show that anti-GlcNAc/anti-myosin mAb 3.B6 from a rheumatic carditis patient was cytotoxic for human endothelial cell lines and reacted with human valvular endothelium and underlying basement membrane. Reactivity of mAb 3.B6 with the valve was inhibited by human cardiac myosin > laminin > GlcNAc. The mAb 3.B6 epitopes were localized in fragments of human cardiac myosin, including heavy meromyosin (HMM), the S1 subfragment, and two light meromyosin (LMM) peptides containing amino acid sequences KEALISSLTRGKLTYTQQ (LMM 1) and SERVQLLHSQNTSLINQK (LMM 33). A novel feature of mAb 3.B6 was its reactivity with the extracellular matrix protein laminin, which may explain its reactivity with the valve surface. A laminin A-chain peptide (HTQNT) that includes homology to LMM33 inhibited the reactivity of mAb 3.B6 with human valve. These data support the hypothesis that cross-reactive antibodies in rheumatic carditis cause injury at the endothelium and underlying matrix of the valve.
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Although the pathogenesis of IAE is still not completely understood, it has been connected to other infection-linked disorders such as rheumatic fever (RF), which can progress to rheumatic heart disease when molecular mimicry and production of antimyocardial antibodies and streptococcal antigens cross-react.
“Although the pathogenesis of IAE is still not completely understood, it has been connected to other infection-linked disorders such as rheumatic fever (RF), which can progress to rheumatic heart disease when molecular mimicry and production of antimyocardial antibodies and streptococcal antigens cross-react.13”
From An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know (2023) · cites this paper as [13]
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Experimental — accuracy not yet measuredThe pathophysiology of IAE is believed to involve an autoimmune process that targets brain structures including the basal ganglia, leading to neuroinflammation and subsequent neuropsychiatric symptoms.
“The pathophysiology of IAE is believed to involve an autoimmune process that targets brain structures including the basal ganglia, leading to neuroinflammation and subsequent neuropsychiatric symptoms.”
From An updated review of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus/pediatric acute-onset neuropsychiatric syndrome, also known as idiopathic autoimmune encephalitis: What the allergist should know (2023) · cites this paper as [13]
The Introduction and Discussion describe cross-reactive antibodies in rheumatic carditis and possible inflammation of heart valves. The Introduction mentions chorea as a manifestation of rheumatic fever, but the copy does not address IAE, basal ganglia targeting, neuroinflammation, or the proposed pathway to neuropsychiatric symptoms (searched: IAE, brain structures, basal ganglia, neuropsychiatric symptoms). (LLM, conf=0.76)
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Cardiac myosin-Th17 responses promote heart failure in human myocarditis
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- Authors
- Galvin, J. E., Hemric, M. E., Ward, K., & Cunningham, M. W.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Cunningham, Madeleine W.
- Venue
- Journal of Clinical Investigation
- Published
- 2000-07-15
- Volume
- 106
- Issue
- 2
- Pages
- 217-224
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC314302
- OpenAlex
- W2075460902
- Cited by
- 248
- References
- 46
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 7 · 2023: 11 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 10 · 2018: 11 · 2017: 9 · 2016: 15 · 2015: 6 · 2014: 13 · 2013: 10 · 2012: 7
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons (Liberty University) (submittedVersion)
- Funders
- University of Oklahoma
- University of Oklahoma Health Sciences Center
- National Heart, Lung, and Blood Institute (R56HL056267, R01HL056267, R37HL035280, HL-56267, HL35280)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Keywords
- rheumatic carditis, rheumatic fever, streptococcal antibodies, anti-myosin antibodies, cytotoxic antibodies, heart valves, laminin, cardiac myosin, light meromyosin, heavy meromyosin, basement membrane, extracellular matrix, antibody cross-reactivity, endothelial injury
- MeSH terms
- Acetylglucosamine, Adolescent, Amino Acid Sequence, Antibodies, Monoclonal, Cytotoxicity, Immunologic, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Heart Valves, Humans, Laminin, Male, Molecular Sequence Data, Myocarditis, Myosins, Peptide Fragments, Rheumatic Heart Disease, Epitope Mapping, Molecular Mimicry
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