Identification of Streptococcal M-Protein Cardiopathogenic Epitopes in Experimental Autoimmune Valvulitis

Kirvan, Christine A.; Galvin, Jeffrey E.; Hilt, Silvia; Kosanke, Stanley D.; Cunningham, Madeleine W.

doi:10.1007/s12265-013-9526-4

Cited by 33 publications

(55 citation statements)

References 47 publications

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“…Comparison of the epitopes studied in humans with those found to induce valve lesions in the Lewis rat revealed that the GAS M protein epitopes were similar to those in the human and cross-reacted with cardiac myosin (17–20). M protein specific T cell lines were found to home to the valve and induce VCAM-1 expression in a passive T cell transfer model (20).…”

Section: Introductionmentioning

confidence: 87%

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease

et al. 2016

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Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage. We also found evidence that both complement and anti-M protein antibodies in serum from rM5-immunized rats have the potential to contribute to inflammation in heart valves by activating cardiac endothelium. More importantly we have demonstrated by electrocardiography for the first time in the RAV model that elongation of P-R interval follows repetitive boost with rM5. Our observations provide experimental evidence for cardiac alterations following repeat exposure to GAS M protein with immunological and electrophysiological features resembling that seen in humans following recurrent GAS infection.

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Section: Introductionmentioning

confidence: 87%

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease

et al. 2016

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“…For instance, rat T cell lines that are specific for streptococcal M5 protein epitopes such as DKLKQQRDTLSTQKET 134 passively transfer valvulitis and upregulation of VCAM1 (REF. 135) to uninfected rats.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Acute rheumatic fever and rheumatic heart disease

Carapetis

Beaton

Cunningham

et al. 2016

Nat Rev Dis Primers

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Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances — including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life — give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty.

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“…This pathway may be crucial in induction of autoimmunity, which is a major pathogenic factor in cardiac damage. Group A streptococcus, the cause of rheumatic heart disease [40], andCVB3 [36] both induce CD4+ Tcell responses which cross-reactively recognize microbial and heart antigens and can adoptively transfer myocarditis to naive recipients.…”

Section: Myocarditis and Heart Failurementioning

confidence: 99%

Review and Updates in Regenerative and Personalized Medicine, Preclinical Animal Models, and Clinical Care in Cardiovascular Medicine

Barbato

Barton

Bartúnek

et al. 2015

J. of Cardiovasc. Trans. Res.

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The goal of this paper is to provide an updated review for scientists and clinicians on the major areas in cardiovascular medicine published in the Journal. Leading topics in regenerative and personalized medicine are presented along with a critical overview of the field. New standards in large preclinical animal models of pulmonary hypertension and left bundle branch block are highlighted. Finally, clinical care in the areas of atherosclerosis, the aortic valve, platelet biology, and myocarditis is discussed as well as autonomic modulation therapies

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Identification of Streptococcal M-Protein Cardiopathogenic Epitopes in Experimental Autoimmune Valvulitis

Cited by 33 publications

References 47 publications

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease

Acute rheumatic fever and rheumatic heart disease

Review and Updates in Regenerative and Personalized Medicine, Preclinical Animal Models, and Clinical Care in Cardiovascular Medicine

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