Anti-Cardiac Troponin Autoantibodies Are Specific to the Conformational Epitopes Formed by Cardiac Troponin I and Troponin T in the Ternary Troponin Complex

Clin Chem. 2017 Jan;63(1):343-350. doi: 10.1373/clinchem.2016.261602. Epub 2016 Nov 4.

Abstract

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.

MeSH terms

  • Acute Disease
  • Adult
  • Antigen-Antibody Reactions
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Epitopes / blood
  • Epitopes / immunology*
  • Healthy Volunteers
  • Humans
  • Immunoassay
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / immunology*
  • Troponin I / blood
  • Troponin I / immunology*
  • Troponin T / blood
  • Troponin T / immunology*
  • Young Adult

Substances

  • Autoantibodies
  • Epitopes
  • Troponin I
  • Troponin T