Influence of biological variations of cardiac troponin on the quantification in clinical context

• Applicant: Dr. Claudia Swart
• Subject Area: Cardiology, Angiology ; Analytical Chemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539926295

Around 70 % of medical decisions depend on in vitro diagnostics measurements. Therefore, it is essential that these diagnostics provide reliable results irrespective of the analysing laboratory. However, proficiency testing schemes show that results obtained with different measurement platforms are often not comparable. One solution is traceability to a reference measurement procedure. However, before such a procedure can be developed it is essential to understand what the in vitro diagnostic platforms really measure, so that a common measurand can be defined, and influences on the accuracy are understood. This project aims to investigate the influence of biological modifications of cardiac troponin (cTn) on the results of both immunoassays and potential reference measurement procedures. cTn was chosen as an analyte due to its importance in the diagnoses of heart diseases such as myocardial infarction.The major known modifications of cTn in clinical samples are phosphorylation and the formation of complexes of the various cTn subunits (cTnI-C, cTnI-T, cTnI-T-C) with each other and/or with autoantibodies. Starting with recombinant cTnI without any post-translational modifications, cTnI will be produced with defined phosphorylation and characterise thoroughly regarding number of modifications, modification sites and their impact on the different measurement procedures. This project will pay special attention on the antibodies used for capture and/or detection in immunoassays and enrichment procedures because these are responsible if a method fails or not. Another focus of the project will be the investigation of the effect of so-called macroptroponin on the results in routine measurements as well as the potential reference measurement procedures. Macrotroponin is formed when cTnI binds to autoantibodies in the blood of patients. Especially patients with a history of heart diseases have autoantibodies against cTnI in their blood (according to literature between 5 % and 53 %). A method to identify and quantify these complexes will be developed. With the knowledge of the composition of macrotroponin, cTnI-antibody complexes will be produced that behaves similar to macrotroponin and can serve as interference control material. Based on the results from the studies on phosphorylated cTn and macrotroponin, a material will be developed and evaluated regarding its ability to be used as a primary calibrator for the determination of cTn and macrotroponin. Furthermore, the methods developed within this project will then be used to investigate cTn forms present in the candidate calibration materials provided by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).The outcome of this project will enable a better definition of the measurand and, thus, help to improve the reliability of measurement procedures. More reliable measurements results will in turn improved diagnosis, which will finally serve the patients.

• DFG Programme: Research Grants
• International Connection: Turkey
• Partner Organisation: TÜBITAK The Scientific and Technology Research Council of Turkey
• Cooperation Partner: Dr. Merve Öztug Kilinc