Autoantibodies to cardiac troponin I in patients with idiopathic dilated and ischemic cardiomyopathy

Shmilovich, Haim; Danon, Asaf; Binah, Ofer; Roth, Arie; Chen, Gerald; Wexler, Dov; Keren, Gad; George, Jacob

doi:10.1016/j.ijcard.2006.04.077

Cited by 60 publications

(64 citation statements)

References 22 publications

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“…In general, autoantibodies which form macroanalyte complexes are not believed to be disease-causing although cases associated with autoimmune disorders have been described [16,17] and reports suggesting an association between the presence of autoantibodies against cTnI and cardiomyopathy have been published [18][19][20]. Based on current evidence, the main problem caused by a circulating macroanalyte is that it leads to multiple, possibly invasive, investigations in search of a cause.…”

Section: Introductionmentioning

confidence: 99%

High incidence of macrotroponin I with a high-sensitivity troponin I assay

Warner

Marshall

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background:Cardiac troponin is the preferred biomarker of myocardial injury. High-sensitivity troponin assays allow measurement of very low levels of troponin with excellent precision. After the introduction of a high-sensitivity troponin I assay the laboratory began to receive enquiries from clinicians about clinically discordant elevated troponin I results. This led to a systematic investigation and characterisation of the cause.Methods:Routine clinical samples were measured by the Architect High Sensitive Troponin-I (hsTnI) and the VITROS Troponin I ES assays (VitrosTnI). Results that were elevated according to the Architect but not the VITROS assay (Group 1) or results elevated by both assays but disproportionately higher on the Architect (Group 2) were re-analysed for hsTnI after re-centrifugation, multiple dilutions, incubation with heterophilic blocking reagents, polyethylene glycol (PEG) precipitation, and Protein A/G/L treatment. Sephacryl S-300 HR gel filtration chromatography (GFC) was performed on selected specimens.Results:A high molecular weight complex containing immunoreactive troponin I and immunoglobulin (macrotroponin I) was identified in 5% of patients with elevated hsTnI. Patients with both macrotroponin and myocardial injury had higher and longer elevation of hsTnI compared with VitrosTnI with peaks of both macrotroponin and free troponin I-C complex on GFC.Conclusions:Circulating macrotroponin I (macroTnI) causes elevated hsTnI results with the Architect High Sensitive Troponin-I assay with the potential to be clinically misleading. The assay involved in this investigation may not be the only assay affected by macrotroponin. It is important for laboratories and clinicians to be aware of and develop processes to identify and manage specimens with elevated results due to macrotroponin.

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Section: Introductionmentioning

confidence: 99%

High incidence of macrotroponin I with a high-sensitivity troponin I assay

Warner

Marshall

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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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%

“…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 carried out in cultured neonatal rat ventricular myocytes, anti-cardiac troponin I autoantibodies obtained from human patients were unable to bind to cardiomyocytes or to influence calcium transients (9). Halley et al described a heightened cellular interleukin-10 response of peripheral blood mononuclear cells to cardiac troponin I in a subset of patients with idiopathic DCM, in association with reduced systemic levels of C-reactive protein and a lower prevalence of advanced diastolic dysfunction (10).…”

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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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“…Num trabalho de Shmilovich et al 7 três grupos de indivíduos foram testados, dois deles com miocardiopatia dilatada (de etiologia isquémica em 33 casos e não isquémica em 32) e um deles composto por 42 indivíduos saudáveis. A presença de autoanticorpos IgG antitroponina I foi encontrada em 18,2% dos casos de natureza isquémica e 15,6% nos casos de etiologia não isquémica, sem que se identificassem em qualquer caso de indivíduos normais.…”

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Autoanticorpos antitroponina cardíaca em doentes após transplante renal. Um novo alvo para a terapêutica com estatinas?

Morais

2015

Revista Portuguesa de Cardiologia

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Disponível na Internet a 2 de fevereiro de 2015A resposta imunitária em situações de agressão ao músculo cardíaco é uma matéria pouco estudada e de resultados práticos pouco relevantes. Mesmo na situação do enfarte do miocárdio, o paradigma da agressão ao miocárdio por razões não infecciosas ou inflamatórias, o impacto clínico dessa investigação é muito reduzido.Um exemplo do que se pode esperar deste tipo de investigação, com potencial reflexo para a atividade clínica, é a recente publicação de um interessante trabalho de Savukoski et al. procurando ensaiar um novo teste laboratorial para determinação de troponina, o qual possa ser livre da interferência de eventuais autoanticorpos antitroponina que possam estar presentes em circulação 1 .A presença destes autoanticorpos específicos foi investigada por este mesmo grupo, o qual demonstrou, numa série de 510 doentes com suspeita de enfarte do miocárdio, a presença de autoanticorpos em 9,2% dos casos, sem contudo se encontrar qualquer reflexo sobre o prognóstico a 12 meses 2 .O aspeto prático desta observação reside no facto de que a presença destes anticorpos pode conduzir a valores falsamente negativos de troponina no soro de doentes com enfarte do miocárdio e desse modo pode contribuir para o atraso no diagnóstico.DOI do artigo original: http://dx.doi.org/10.1016/j.repc.2014.08.018Correio eletrónico: jaraujomorais@mail.telepac.pt A sua presença em indivíduos aparentemente saudáveis também foi relatada. Há alguns anos atrás Adamczyk et al. 3 reportaram uma prevalência de 12,7% de autoanticorpos em indivíduos saudáveis, dadores de sangue, sem diferenças significativas no que respeita às isoformas T ou I.Esta resposta imunitária pode ser parcialmente neutralizada, através da administração por via nasal das três subunidades de troponina (C, I e T) e essa neutralização/vacinação pode ter efeito na redução do tamanho do enfarte, quando a referida administração se processa uma hora antes do fenó-meno isquemia/reperfusão 4 .Um outro campo de interesse e que igualmente tem despertado algum interesse dos investigadores é a presença do mesmo tipo de autoanticorpos em doentes com miocardiopatia dilatada. A distrofia muscular de Emery-Dreifuss é um bom exemplo.Tratando-se de uma doença rara, em alguns casos a doença é detetada através da presença de um quadro de miocardiopatia dilatada, casos estes em que o envolvimento do músculo cardíaco precede o envolvimento dos múscu-los esqueléticos. Num estudo de dez doentes, avaliados em comparação com um grupo de controlo emparelhado para algumas características, foi possível perceber que não há uma relação clara entre níveis de anticorpos e sintomatologia cardíaca, se bem que os autores admitam que a sua deteção pode representar um marcador de previsão de está-dios precoces de miocardiopatia dilatada 5 .A autoimunidade tem o seu lugar na patogénese de algumas entidades como sejam a miocardiopatia dilatada, as http://dx

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Autoantibodies to cardiac troponin I in patients with idiopathic dilated and ischemic cardiomyopathy

Cited by 60 publications

References 22 publications

High incidence of macrotroponin I with a high-sensitivity troponin I assay

High incidence of macrotroponin I with a high-sensitivity troponin I assay

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

Autoanticorpos antitroponina cardíaca em doentes após transplante renal. Um novo alvo para a terapêutica com estatinas?

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