Rafeek, Rukshan A M

Hamlin, Adam S

Andronicos, Nicholas M

Lawlor, Craig S

McMillan, David J

Sriprakash, S Kadaba

Ketheesan, Natkuman

2022-09

<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>

Immunology and Cell Biology, 100(8), p. 653-666

1440-1711

0818-9641

35792671

https://hdl.handle.net/1959.11/69019

en

John Wiley & Sons Ltd

Attribution-NonCommercial-NoDerivatives 4.0 International

Autoimmunity

Lewis rat model

Streptococcus dysgalactiae subspecies equisimilis

group A streptococcus

rheumatic heart disease

sydenham chorea

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

Journal Article

Publication