Anti-Cardiac Troponin Autoantibodies Are Specific to the Conformational Epitopes Formed by Cardiac Troponin I and Troponin T in the Ternary Troponin Complex.
BACKGROUND
Autoantibodies to cardiac troponins (TnAAbs) could negatively affect cardiac troponin I (cTnI) measurements by TnAAbs-sensitive immunoassays. We investigated the epitope specificity of TnAAbs and its influence on cTnI immunodetection in patients with acute myocardial infarction (AMI).


METHODS
The specificity of TnAAbs was studied in immunoassays and gel-filtration experiments. The influence of TnAAbs on endogenous troponin measurements was studied in 35 plasma samples from 15 patients with AMI.


RESULTS
The inhibitory effect of TnAAbs on the cTnI immunodetection was observed only for the ternary cardiac troponin complex (I-T-C) and not for the binary cardiac troponin complex (I-C) or free cTnI. In the same TnAAbs-containing samples, the immunodetection of cardiac troponin T (cTnT) added in the form of I-T-C (but not free cTnT) was also inhibited in the assays that used monoclonal antibodies (mAbs) specific to the 223-242 epitope. The negative effects of TnAAbs on the measurements of endogenous cTnI in AMI samples were less than on the measurements of isolated I-T-C and decreased with time after the onset of symptoms. Early AMI blood samples might contain a mixture of the I-T-C and I-C complexes with the ratio gradually changing with the progression of the disease in favor of I-C.


CONCLUSIONS
The investigated TnAAbs are specific to the structural epitopes formed by cTnI and cTnT molecules in the I-T-C complex. AMI blood samples contain a mixture of I-C and I-T-C complexes. The concentrations of total cTnI at the early stage of AMI could be underestimated in approximately 5%-10% of patients if measured by TnAAbs-sensitive immunoassays.
HyTest Ltd. Research and Development Department, Turku, Finland; alexandra.vylegzhanina@hytest.fi.
Alexandra V
AV
Vylegzhanina
HyTest Ltd. Research and Development Department, Turku, Finland.|Departments of Bioorganic Chemistry and.
Alexander E
AE
Kogan
HyTest Ltd. Research and Development Department, Turku, Finland.|Biochemistry, School of Biology, Moscow State University, Moscow, Russia.
Ivan A
IA
Katrukha
Departments of Bioorganic Chemistry and.
Olga V
OV
Antipova
Biochemistry, School of Biology, Moscow State University, Moscow, Russia.
Andrey N
AN
Kara
HyTest Ltd. Research and Development Department, Turku, Finland.|Departments of Bioorganic Chemistry and.
Anastasia V
AV
Bereznikova
67th City Hospital, Moscow, Russia.
Ekaterina V
EV
Koshkina
HyTest Ltd. Research and Development Department, Turku, Finland.|Biochemistry, School of Biology, Moscow State University, Moscow, Russia.
Alexey G
AG
Katrukha
D000208:Acute Disease; D000328:Adult; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000097:blood / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D019210:Troponin I / Q000097:blood / Q000276:immunology*; D020107:Troponin T / Q000097:blood / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D000939:Epitopes; D019210:Troponin I; D020107:Troponin T