Impact of troponin I-autoantibodies in chronic dilated and ischemic cardiomyopathy

Doesch, Andreas O.; Mueller, Susanne; Nelles, Manfred; Konstandin, Mathias; Celik, Sultan; Frankenstein, Lutz; Goeser, Stefan; Kaya, Ziya; Koch, Achim; Zugck, Christian; Katus, Hugo A.

doi:10.1007/s00395-010-0126-z

Cited by 39 publications

(38 citation statements)

References 25 publications

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“…Most studies assessed anti-troponin I antibodies (9,12,14,(39)(40)(41)(42)(45)(46)(47)(48)50,51,(53)(54)(55)(56)(57)(58), whereas anti-troponin T antibodies were assessed in only 16% (n=1,636) of individuals (11,43,44,49,52) (including 993 individuals where both types of autoantibodies were evaluated) (11,44,49).…”

Section: Resultsmentioning

confidence: 99%

“…Over half of the studies included assessed individuals with cardiovascular diseases (9,11,12,14,39,40,(44)(45)(46)(47)(48)50,51,53,(55)(56)(57), especially DCM. The prevalence of anti-troponin I autoantibodies in DCM ranged from 7.0% (11) to 22.2% (in patients prior to immunoadsorption, notably decreased to 3.7% after immunoadsorption) (53).…”

Section: Resultsmentioning

confidence: 99%

“…The authors reported superior survival in patients with DCM when compared to ICM, and the presence of autoantibodies in plasma was associated with an improved survival in patients with chronic DCM (though not in ICM) (12).…”

Section: Heart Failure Including Dcm and Icmmentioning

confidence: 95%

“…In another study, Doesch et al [2011] studied the prognostic impact of anti-troponin I antibodies in HF patients (12). The authors reported superior survival in patients with DCM when compared to ICM, and the presence of autoantibodies in plasma was associated with an improved survival in patients with chronic DCM (though not in ICM) (12).…”

Section: Heart Failure Including Dcm and Icmmentioning

confidence: 99%

“…Leuschner et al showed that the absence of autoantibodies against cardiac troponin I predicted an improvement of left ventricular function after an acute myocardial infarction (MI) (11). Doesch et al, however, described a beneficial effect of anti-troponin I autoantibodies in the setting of DCM (improved survival), but not in patients with ICM (12). Thus, although having been described over 20 years ago (initially as a source of potentially falsenegative immunoassay results), the specific role of these autoantibodies, if any, remains elusive (13,14).…”

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confidence: 99%

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Anti-cardiac troponin antibodies in clinical human disease: a systematic review

Vilela¹,

Bettencourt‐Silva²,

Costa³

et al. 2017

Ann. Transl. Med.

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Anti-cardiac troponin antibodies have been studied in different types of clinical diseases and in healthy populations. A systematic review of published data on anti-troponin antibodies was carried out (search performed on PubMed, ISI Web of Knowledge and Scopus databases). From title and abstract analysis, thirty-three articles were included that met the pre-specified criteria; after full-text analysis, nine articles were excluded. Most studies assessed anti-troponin I antibodies. The prevalence of anti-cardiac troponin antibodies in healthy individuals ranged from 0.0% to 20.0%. The prevalence of anti-troponin I autoantibodies in dilated cardiomyopathy (DCM) ranged from 7.0% to 22.2%. Other conditions under study were myocardial infarction, ischemic cardiomyopathy (ICM), peripartum cardiomyopathy (PPCM), Chagas disease, Emery-Dreifuss muscular dystrophy (EDMD) and renal transplantation. In the different patient populations studied, anti-cardiac troponin antibodies have been shown to be either positively or negatively associated with prognostic and clinical features. In what concerns a possible value as biomarkers, these assays have not emerged up to the present moment as important aids for practical clinical decisions in cardiac or other types of patients. In what concerns pathophysiology, anti-cardiac troponin autoantibodies may play a role in different diseases. It can be speculated that these antibodies could be involved in perpetuating some degree of cardiac injury after an event, such as myocardial infarction or PPCM. The major function of the heart is its contractile function, and cardiac muscle contains sarcomeres, which include different types of molecules, of which actin and myosin are essential for strength generation during contraction. Other molecules, such as cardiac troponins, play a role of regulation concerning cardiac muscle contraction. Cardiac troponins I and T have been shown to be different molecules than the corresponding ones in skeletal muscle, and have gained importance as cardiac biomarkers (1,2).Research has shown that antibodies against cardiac troponins exist in different settings, and questions about their role in the cardiovascular pathological continuum have emerged over the last years. The possible role of cardiac troponin autoantibodies in disease processes [and particularly in dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM)] has gained interest (3-6).Animal models in mice have demonstrated that anticardiac troponin I autoantibodies are capable of inducing heart dilatation and dysfunction, apparently through interactions with the calcium balance in cardiomyocytes (7). Okazaki et al. showed that in mice antibodies to cardiac troponin I stained the surface of cardiomyocytes, implying the presence of troponin I on the cell surface (differing from cardiac troponin T) (7). Göser et al. immunized mice with cardiac troponin I, leading to severe inflammation of the myocardium, cardiomegaly, fibrosis and 30% mortality over 270 days (8). However, in a study carri...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Heart Failure Including Dcm and Icmmentioning

confidence: 95%

Section: Heart Failure Including Dcm and Icmmentioning

confidence: 99%

mentioning

confidence: 99%

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Anti-cardiac troponin antibodies in clinical human disease: a systematic review

Vilela¹,

Bettencourt‐Silva²,

Costa³

et al. 2017

Ann. Transl. Med.

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The role of B cells in heart failure and implications for future immunomodulatory treatment strategies

et al. 2020

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Despite numerous demonstrations that the immune system is activated in heart failure, negatively affecting patients' outcomes, no definitive treatment strategy exists directed to modulate the immune system. In this review, we present the evidence that B cells contribute to the development of hypertrophy, inflammation, and maladaptive tissue remodelling. B cells produce antibodies that interfere with cardiomyocyte function, which culminates as the result of recruitment and activation of a variety of innate and structural cell populations, including neutrophils, macrophages, fibroblasts, and T cells. As B cells appear as active players in heart failure, we propose here novel immunomodulatory therapeutic strategies that target B cells and their products.

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Surviving the infarct: A profile of cardiac myosin binding protein‐C pathogenicity, diagnostic utility, and proteomics in the ischemic myocardium

Lynch

Sadayappan

2014

Proteomics Clinical Apps

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Summary Cardiac myosin binding protein-C (cMyBP-C) is a regulatory protein of the contractile apparatus within the cardiac sarcomere. Ischemic injury to the heart during myocardial infarction (MI) results in the cleavage of cMyBP-C in a phosphorylation-dependent manner and release of an N-terminal fragment (C0C1f) into the circulation. C0C1f has been shown to be pathogenic within cardiac tissue, leading to the development of heart failure (HF). Based on its high levels and early release into the circulation post-MI, C0C1f may serve as a novel biomarker for diagnosing MI more effectively than current clinically used biomarkers. Over time, circulating C0C1f could trigger an autoimmune response leading to myocarditis and progressive cardiac dysfunction. Given the importance of cMyBP-C phosphorylation state in the context of proteolytic cleavage and release into the circulation post-MI, understanding the post-translational modifications (PTMs) of cMyBP-C would help in further elucidating the role of this protein in health and disease. Accordingly, recent studies have implemented the latest proteomics approaches to define the PTMs of cMyBP-C. The use of such proteomics assays may provide accurate quantitation of the levels of cMyBP-C in the circulation following MI, which could, in turn, demonstrate the efficacy of using plasma cMyBP-C as a cardiac-specific early biomarker of MI. In this review, we define the pathogenic and potential immunogenic effects of C0C1f on cardiac function in the post-MI heart. We also discuss the most advanced proteomics approaches now used to determine cMyBP-C PTMs with the aim of validating C0C1f as an early biomarker of MI.

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Impact of troponin I-autoantibodies in chronic dilated and ischemic cardiomyopathy

Cited by 39 publications

References 25 publications

Anti-cardiac troponin antibodies in clinical human disease: a systematic review

Anti-cardiac troponin antibodies in clinical human disease: a systematic review

The role of B cells in heart failure and implications for future immunomodulatory treatment strategies

Surviving the infarct: A profile of cardiac myosin binding protein‐C pathogenicity, diagnostic utility, and proteomics in the ischemic myocardium

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