Degradation of cardiac troponin I in serum complicates comparisons of cardiac troponin I assays

Citation
Qw. Shi et al., Degradation of cardiac troponin I in serum complicates comparisons of cardiac troponin I assays, CLIN CHEM, 45(7), 1999, pp. 1018-1025
Citations number
31
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
CLINICAL CHEMISTRY
ISSN journal
00099147 → ACNP
Volume
45
Issue
7
Year of publication
1999
Pages
1018 - 1025
Database
ISI
SICI code
0009-9147(199907)45:7<1018:DOCTII>2.0.ZU;2-M
Abstract
Background: Up to a 20-fold variation in serum cardiac troponin I (cTnI) co ncentration may be observed for a given patient sample with different analy tical methods. Because more limited variation is seen for control materials and for purified cTnI, we explored the possibility that cTnI was present i n altered forms in serum. Methods: We used four recombinantly engineered cTnI fragments to study the regions of cTnI recognized by the Stratus(R), Opus(R), and ACCESS(R) immuno assays. The stability of these regions in serum was analyzed with Western b lot. Results: The measurement of several control materials and different forms o f purified cTnI using selected commercial assays demonstrated five- to nine fold variation. Both the Stratus and Opus assays recognized the N-terminal portion (NTP) of cTnI, whereas the ACCESS assay recognized the C-terminal p ortion (CTP) of cTnI. Incubation of recombinant cTnI in normal human serum produced a marked decrease in cTnI concentration as determined with the ACC ESS, but not the Stratus, immunoassay. Western blot analysis of the same sa mples using cTnI NTP- and CTP-specific antibodies demonstrated preferential degradation of the CTP of cTnI. Conclusions: The availability of serum cTnI epitopes is markedly affected b y the extent of ligand degradation. The N-terminal half of the cTnI molecul e was found to be the most stable region in human serum. Differential degra dation of cTnI is a key factor in assay-to-assay variation. (C) 1999 Americ an Association for Clinical Chemistry.