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Immunity Inflam Disease - 2025 - Rafeek - Inflammatory Responses Potentiate GAS M Protein Induced Cardiac Damage in an2.68 MB
Published VersionCC BY V4.0, Open Access
Journal article
Inflammatory Responses Potentiate GAS M Protein Induced Cardiac Damage in an Experimental Model of Rheumatic Heart Disease
Immunity, Inflammation and Disease, Vol.13(7), pp.1-15
2025
PMID: 40642941
Abstract
Acute 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.
To 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.
Lewis 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.
These 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.
Details
- Title
- Inflammatory Responses Potentiate GAS M Protein Induced Cardiac Damage in an Experimental Model of Rheumatic Heart Disease
- Authors
- Rukshan A M Rafeek (Corresponding Author) - University of New EnglandSimone L Reynolds - QIMR Berghofer Medical Research InstituteManisha Pandey - Griffith UniversityDavid J McMillan - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringKadaba S Sriprakash - University of New EnglandMichael F Good - Griffith UniversityNatkunam Ketheesan (Corresponding Author) - University of New England
- Publication details
- Immunity, Inflammation and Disease, Vol.13(7), pp.1-15
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2025
- DOI
- 10.1002/iid3.70221
- ISSN
- 2050-4527
- PMID
- 40642941
- Copyright note
- © 2025 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Data Availability
- The data underlying this article are available in the article and in its online supporting information.
- Organisation Unit
- School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991144530002621
- Output Type
- Journal article
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