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Characterization of an experimental model to determine streptococcal M protein–induced autoimmune cardiac and neurobehavioral abnormalities1.23 MB
Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
Characterisation of an experimental model to determine streptococcal M protein induced autoimmune cardiac and neurobehavioral abnormalities
Immunology and Cell Biology, Vol.100(8), pp.653-666
2022
PMID: 35792671
Abstract
Group A streptococcal (GAS) infection is associated with spectrum of autoimmune diseases including Acute Rheumatic Fever/Rheumatic Heart Disease (ARF/RHD) and neurobehavioral abnormalities. Antibodies against GAS M proteins cross-react with host tissue proteins in the heart and brain leading to the symptomatology observed in ARF/RHD. Since throat carriage of Streptococcus dysgalactiae subspecies equisimilis (SDSE) has been reported to be relatively high in some ARF/RHD endemic regions compared to GAS, and both SDSE and GAS express coiled coil surface protein called M protein, we hypothesised that streptococci other than GAS can also associated with ARF/RHD and neurobehavioral abnormalities. Neurobehavioral assessments and electrocardiography were performed on Lewis rats pre and post exposure to recombinant GAS and SDSE M proteins. Histological assessments were performed to confirm inflammatory changes in cardiac and neuronal tissue. ELISA and Western blot analysis were performed to determine the cross-reactivity of antibodies with host connective, cardiac and neuronal tissue proteins. Lewis rats injected with M proteins either from GAS or SDSE developed significant cardiac functional and neurobehavioral abnormalities in comparison to control rats injected with PBS. Antibodies against GAS and SDSE M proteins cross-reacted with cardiac, connective and neuronal proteins. Serum from rats injected with streptococcal antigens showed higher IgG binding to the striatum and cortex of the brain. Cardiac and neurobehavioral abnormalities observed in our experimental model were comparable to the cardinal symptoms observed in patients with ARF/RHD. Here for the first time, we demonstrate in an experimental model that M proteins from different streptococcal species could initiate and drive the autoimmune mediated cardiac tissue damage and neurobehavioral abnormalities.
Details
- Title
- Characterisation of an experimental model to determine streptococcal M protein induced autoimmune cardiac and neurobehavioral abnormalities
- Authors
- Rukshan A Rafeek (Corresponding Author) - University of New EnglandAdam S Hamlin (Author) - University of New EnglandNicholas M Andronicos (Author) - University of New EnglandCraig S Lawlor (Author) - University of New EnglandDavid McMillan (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringKadaba Srinivasa Sriprakash (Author) - University of New EnglandNatkunam Ketheesan (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
- Publication details
- Immunology and Cell Biology, Vol.100(8), pp.653-666
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2022
- DOI
- 10.1111/imcb.12571
- ISSN
- 1440-1711; 0818-9641
- PMID
- 35792671
- Grant note
- National Health and Medical Research Council (APP 2010336)
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99654998902621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Cell Biology
- Immunology
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