Characterization of an experimental model to determine streptococcal M protein–induced autoimmune cardiac and neurobehavioral abnormalities

Author(s)
Rafeek, Rukshan A M
Hamlin, Adam S
Andronicos, Nicholas M
Lawlor, Craig S
McMillan, David J
Sriprakash, S Kadaba
Ketheesan, Natkuman
Publication Date
2022-09
Abstract
<p>Group A streptococcal (GAS) infection is associated with a 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. As throat carriage of <i>Streptococcus dysgalactiae</i> subspecies <i>equisimilis</i> (SDSE) has been reported to be relatively high in some ARF/RHD endemic regions compared with GAS, and both SDSE and GAS express coiled-coil surface protein called M protein, we hypothesized that streptococci other than GAS can also associated with ARF/RHD and neurobehavioral abnormalities. Neurobehavioral assessments and electrocardiography were performed on Lewis rats before and after exposure to recombinant GAS and SDSE M proteins. Histological assessments were performed to confirm inflammatory changes in cardiac and neuronal tissues. 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 phosphate-buffered saline. Antibodies against GAS and SDSE M proteins cross-reacted with cardiac, connective and neuronal proteins. Serum from rats injected with streptococcal antigens showed higher immunoglobulin G 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.</p>
Citation
Immunology and Cell Biology, 100(8), p. 653-666
ISSN
1440-1711
0818-9641
Pubmed ID
35792671
Link
Language
en
Publisher
John Wiley & Sons Ltd
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Subject
Autoimmunity
Lewis rat model
Streptococcus dysgalactiae subspecies equisimilis
group A streptococcus
rheumatic heart disease
sydenham chorea
Title
Characterization of an experimental model to determine streptococcal M protein–induced autoimmune cardiac and neurobehavioral abnormalities
Type of document
Journal Article
Entity Type
Publication

Files:

NameSizeformatDescriptionLink
openpublished/CharacterizationRafeekHamlinAndronicosLawlorMcMillanSriprakashKetheesan2022JournalArticle.pdf 1289.954 KB application/pdf Published Version View document