Multiple immunoassay systems are negatively interfered by circulating cardiac troponin I autoantibodies

Tang, Gusheng; Wu, Yu; Zhao, Weiguo; Shen, Qian

doi:10.1007/s10238-011-0141-x

Cited by 23 publications

(33 citation statements)

References 22 publications

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“…Circulating troponin autoantibodies are not rare, having been identified in 2%-20% of individuals, with or without cardiac disease, in various studies [20][21][22][23][24]. They may be directed towards cTnI [19,22] or cardiac troponin T [20,21].…”

Section: Introductionmentioning

confidence: 99%

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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%

“…Historically, autoantibodies to cTnI have caused negative interference in some cTnI immunoassays [24,25]. Investigation of the epitope specificity of cTnI autoantibodies has shown that the cTnI midfragment (amino acids 30-100) is the commonest target of these antibodies [26,27].…”

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%

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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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Serum miRNA-499 and miRNA-210: A potential role in early diagnosis of acute coronary syndrome

et al. 2016

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In clinical practice, there is still a need for novel biomarkers, which can reliably rule in or rule out acute coronary syndrome (ACS) immediately on admission. This is of particular interest in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) in whom diagnostic uncertainty is high. The aim of the present study is to evaluate the potential role of miRNA-499 and miRNA-210 as novel molecular biomarkers for early diagnosis of UA and NSTEMI suspected patients presented at the emergency unit. A total of 110 patients presenting to the intensive care unit (ICU) within 24 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 37 UA, 48 NSTEMI and 25 noncardiac chest pain (NCCP) patients. Immediately at enrollment, blood samples were taken for estimation of serum miRNA-499 and miRNA-210 expression levels by real time PCR. miRNA-499 and miRNA-210 expression levels were significantly increased in UA and NSTEMI patients compared with NCCP patients (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that the area under curve (AUC) of miR-499 for the diagnosis of UA and NSTEMI was 0.98 and 0.97, respectively; while the AUC of miRNA-210 was 0.84 and 0.90, respectively. The important finding of our study was that the AUC of miRNA-499 for the diagnosis of ACS patients with symptoms onset <3 h was 0.89, while the AUC of miRNA-210 was 0.86. Interestingly, combining miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.96, P < 0.001. In conclusion, serum miRNA-499 and miRNA-210 are associated with UA and NSTEMI and with those presenting within 3 h of symptom onset. Both miRNAs might be potentially novel biomarkers for accelerating the diagnosis of ACS patients in emergency unit. V C 2016 IUBMB Life, 68(8):673-682, 2016

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Multiple immunoassay systems are negatively interfered by circulating cardiac troponin I autoantibodies

Cited by 23 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

Serum miRNA-499 and miRNA-210: A potential role in early diagnosis of acute coronary syndrome

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