ИСТИНА

Background: The measurement of cardiac troponin I (cTnI) in blood is one of the most trusted methods of acute myocardial infarction (AMI) diagnosis. However, in spite of a long history of this biomarker in clinical practice, the selection of antibodies for new generations of cTnI assays remains a complex task. Over the last decade it was shown that the samples of some patients contain autoantibodies that negatively interfere with most of the immunoassay mAbs which are specific to the central (~40-130 amino acid residues, aar) fragment of cTnI (which is considered to be the most stable part of the cTnI molecule). In the current study we aimed: a) to analyze the dynamics of cTnI degradation after AMI, and b) to border cTnI proteolytic fragments that are presented in the circulation of AMI patients in order to determine the epitopes of antibodies that are not significantly influenced by the proteolytic degradation. Methods: Serial blood samples were collected from 66 patients over a period of 1-36 hours following the onset of AMI, both before and after stenting. cTnI and its fragments were studied by Western blotting and fluoroimmunoassay analysis. Results: In the blood of all AMI patients, cTnI was presented by an intact molecule and 11 major fragments with relative molecular masses of 14-24 kDa. Stenting neither affected the repertoire nor the ratio of different cTnI fragments. The ratio of full sized cTnI and its fragments did not change considerably within the first 36 hours after the onset of AMI. mAbs with the epitopes located between ~23-196 aar recognized more than 80% of all detected cTnI. Conclusion: The composition of cTnI fragments in the circulation is mainly constant within the first 36 hours following AMI. More than 80% of all detected fragments comprise 23-196 aar of cTnI which enables the utilization in immunoassays antibodies that are specific to the regions 23-40 and/or 140-196 that are only mildly affected by autoantibody interference.