Negative Interference in Cardiac Troponin I Immunoassays from a Frequently Occurring Serum and Plasma Component

Eriksson, Susann; Junikka, Miia; Laitinen, Päivi; Majamaa‐Voltti, Kirsi; Alfthan, Henrik; Pettersson, Kim

doi:10.1373/49.7.1095

Cited by 92 publications

(73 citation statements)

References 37 publications

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“…Serum samples from one volunteer with constantly low recovery (LR) of added cTnI (Ͻ10%) and serum samples for which cTnI concentrations were correctly measured [normal recovery (NR); mean (SD) recovery, 96 (3.1)%] were obtained from apparently healthy volunteers and from patients without cardiac-related symptoms from Turku University Central Hospital (23 ). Ten selected samples with apparently high amounts of IF on the basis of divergent results with differently configured cTnI immunoassays and a low recovery of cTnI were from a sample panel obtained from 541 consecutive chest pain patients who presented to Turku University Central Hospital (26 ).…”

Section: Materials and Methods Samplesmentioning

confidence: 99%

“…False-negative results have been attributed to bilirubin, hemoglobin (21 ), and in one case, to circulating cTnI autoantibodies (22 ). When performing recovery studies with a cTnI immunoassay, we previously observed frequent negative interference from a serum-and plasmaderived component found in both healthy individuals and patients with acute coronary syndromes (23 ). Further investigation showed that this interfering factor (IF), with an apparent molecular mass of 50 -200 kDa, blocks the binding of antibodies to the central part of cTnI (24 ).…”

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confidence: 99%

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Negative Interference in Cardiac Troponin I Immunoassays by Circulating Troponin Autoantibodies

et al. 2005

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Background: There are numerous potential sources of interference in immunoassays. Our aim was to identify the blood component that causes negative interference in cardiac troponin I (cTnI) immunoassays based on antibodies against the central part of cTnI. Methods: We isolated an interfering factor (IF) from a sample with low recovery of added cTnI, using several consecutive purification steps: caprylic acid precipitation, ammonium sulfate precipitation, and purification on Cibacron Blue gel and protein G columns. Purified IF was identified by gel electrophoresis and mass spectrometric analysis of protein bands. For the direct detection of human antibodies to cardiac troponin in serum samples, we developed immunoassays using three different anti-human immunoglobulin antibodies and measured troponin antibodies in samples with low and normal cTnI recovery. Results: Treatment with caprylic acid did not precipitate IF, but IF precipitated at 40% ammonium sulfate saturation. IF bound to a Cibacron Blue gel column, from which it was eluted with a linear salt gradient; it also bound to protein G. Gel electrophoresis of purified IF showed two major bands with molecular masses corresponding to the heavy (ϳ50 kDa) and light chains (ϳ25 kDa) of immunoglobulin, and their identities were confirmed by mass spectrometry. The presence of troponin-specific autoantibodies was confirmed in samples with low recoveries of cTnI by three different immunoassays. The median signals were significantly

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Section: Materials and Methods Samplesmentioning

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confidence: 99%

Negative Interference in Cardiac Troponin I Immunoassays by Circulating Troponin Autoantibodies

et al. 2005

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“…In previous communications, we have shown that autoantibodies to cTn (cTnAAbs) are commonly found in both healthy control subjects and hospitalized patients with or without a history of cardiac disease (7)(8)(9). Localization of the site in the cTnI molecule prone to autoantibody interference has revealed that the stable midfragment of cTnI (aa 30 -110), especially its C-terminal part, is the most commonly affected region (10 ).…”

confidence: 99%

Autoantibodies to Cardiac Troponin Associate with Higher Initial Concentrations and Longer Release of Troponin I in Acute Coronary Syndrome Patients

Pettersson

Eriksson²,

Wittfooth

et al. 2009

Clinical Chemistry

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BACKGROUND: Cardiac troponin (cTn) is an established marker of myocardial infarction. Pronounced heterogeneity and the minute amounts released into the circulation constitute significant challenges for cTn detection. Recently, autoantibody formation to cTn was shown to be common and to interfere with immunoassay performance. In this study, we investigated cTn autoantibodies and cardiac troponin I (cTnI) in acute coronary syndrome (ACS) patients over a 1-year period after the index event.

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“…After full-text analysis, nine articles were excluded. Of these, six did not specify that anti-cardiac troponin was assessed (30)(31)(32)(33)(34)(35), one did not specify that anti-troponin autoantibodies were assessed (referring only anti-heart autoantibodies) (36), and two were mainly concerned with the characterization of antitroponin autoantibodies (37,38). A flowchart showing the literature search method, as well as the resulting number of articles selected, is displayed in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

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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Negative Interference in Cardiac Troponin I Immunoassays from a Frequently Occurring Serum and Plasma Component

Cited by 92 publications

References 37 publications

Negative Interference in Cardiac Troponin I Immunoassays by Circulating Troponin Autoantibodies

Negative Interference in Cardiac Troponin I Immunoassays by Circulating Troponin Autoantibodies

Autoantibodies to Cardiac Troponin Associate with Higher Initial Concentrations and Longer Release of Troponin I in Acute Coronary Syndrome Patients

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

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