Evidence map›Paper›PMID 40642941›Full record

ArticleImmunity, inflammation and disease2025

Inflammatory Responses Potentiate GAS M Protein Induced Cardiac Damage in an Experimental Model of Rheumatic Heart Disease.

Rukshan A M Rafeek, Simone L Reynolds, Manisha Pandey, David J McMillan, Kadaba S Sriprakash, Michael F Good, Natkunam Ketheesan

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Article in Immunity, inflammation and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Rukshan A M RafeekSchool of Science & Technology, University of New England, Armidale, New South Wales, Australia.ORCID 0000-0001-7190-9666
Simone L ReynoldsInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, Queensland, Australia.
Manisha PandeyInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, Queensland, Australia.
David J McMillanSchool of Science & Technology, University of New England, Armidale, New South Wales, Australia.
Kadaba S SriprakashSchool of Science & Technology, University of New England, Armidale, New South Wales, Australia.
Michael F GoodInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, Queensland, Australia.
Natkunam KetheesanSchool of Science & Technology, University of New England, Armidale, New South Wales, Australia.

Funding

This study was supported by an Ideas Grant (APP2010336) from National Health and Medical Research Council (NHMRC) Australia.
6 · The paper itself

Abstract

aimAcute rheumatic fever (ARF) and Rheumatic heart disease (RHD) are autoimmune sequalae, that develops in a proportion of individuals exposed to group A streptococcal infection. The autoimmune pathology of ARF/RHD is multifactorial. Both host and pathogen-associated factors including genetic predisposition, inflammatory responses, tissue cross-reactive antibodies and T-cells contribute to disease development and progression. Hitherto, the role of inflammatory responses in ARF/RHD has never been demonstrated in animal models. In this study for the first time, using the Rat Autoimmune valvulitis model of RHD, we demonstrate the requirement for inflammatory responses in promoting cardiac damage in ARF/RHD.

methodsTo determine the role of inflammatory responses we used Bordetella pertussis toxin (BPTx) as an adjuvant to enhance the inflammatory responses initiated by GAS M protein.

resultsLewis rats injected with GAS rM5 emulsified in Complete Freund's Adjuvant (CFA) and co-adjuvant BPTx, had enhanced valvulitis and inflammatory changes as shown by; (a) elevated levels of circulating inflammatory cytokines; (b) functional changes characterized by a prolonged P-R interval in electrocardiography, (c) enhanced cross-reactive antibody production against cardiac and connective tissue proteins; and (d) increased infiltration of IFN-γ+ and IL-17A+ secreting leukocytes into myocardium and valvular tissues.

conclusionThese studies have established that in addition to exposure to GAS M protein, BPTx accelerate the inflammatory and autoimmune processes leading to cardiac damage. These observations substantiate the hypothesis that, in susceptible individuals robust inflammatory responses facilitate the progression of ARF/RHD.

Indexed as

Antigens, BacterialBacterial Outer Membrane ProteinsCarrier ProteinsInflammationRheumatic Heart DiseaseStreptococcus pyogenesAnimalsCytokinesDisease Models, AnimalFreund's AdjuvantInterleukin-17MalePertussis ToxinRatsRats, Inbred LewAntigens, BacterialBacterial Outer Membrane ProteinsCarrier ProteinsCytokinesFreund's AdjuvantInterleukin-17Pertussis Toxinstreptococcal M proteinacute rheumatic feveranimal modelpertussis toxinrheumatic heart disease

Identifiers

PMID40642941
PMCPMC12246833

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.