Circulating Cardiac Troponin‐I Autoantibodies in Human Plasma and Serum

Adamczyk, Maciej; Brashear, R. Jeffrey; Mattingly, Phillip G.

doi:10.1111/j.1749-6632.2009.04617.x

Cited by 49 publications

(44 citation statements)

References 18 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%

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%

“…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).Autoantibodies can play different roles in autoimmune diseases. They can be useful for diagnostic purposes, as markers of disease activity and in some cases for establishing prognosis (15,16).…”

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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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“…All of these patients were negative for stroke, cerebral ischemia, seizures, myocarditis, pulmonary infarction, celiac disease, renal failure, hypothyroidism, musculoskeletal diseases, viral infection or fever, connective tissue disorder and burns. If HetAbs or cTnAAbs are present, false cTnI values may occur [26][27][28]. Apart from testing the NORM pool for cTnAAbs and HetAbs by assessment of dilutional underrecovery of a high concentration cTnI pool in NORM pool or by an elevated value above an assay's limit of detection, of which none were observed for any of the 16 assays employed in the study, there was insufficient sample volume remaining to similarly test problematic patient samples further.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of standardization capability of current cardiac troponin I assays by a correlation study: results of an IFCC pilot project

Tate

Bunk

Christenson

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: As a part of an International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) project to prepare a commutable reference material for cardiac troponin I (cTnI), a pilot study evaluated current cTnI assays for measurement equivalence and their standardization capability. Methods: cTnI-positive samples collected from 90 patients with suspected acute myocardial infarction were assessed for method comparison by 16 cTnI commercial assays according to predefined testing protocols. Seven serum pools prepared from these samples were also assessed. Results: Each assay was assessed against median cTnI concentrations measured by 16 cTnI assays using PassingBablok regression analysis of 79 patient samples with values above each assay's declared detection limit. We

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Circulating Cardiac Troponin‐I Autoantibodies in Human Plasma and Serum

Cited by 49 publications

References 18 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

Evaluation of standardization capability of current cardiac troponin I assays by a correlation study: results of an IFCC pilot project

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