Assay for cardiac troponin autoantibodies
First Claim
1. A method of determining the reliability of a cardiac troponin antigen assay in a biological sample from a subject, the method comprisingassaying the biological sample from the subject for an autoantibody reactive with the cardiac troponin antigen being assayed, to allow detection of an elevated level of the cardiac troponin-reactive autoantibody against the cardiac troponin antigen in the biological sample in comparison to a predetermined normal control sample having normal values of cardiac troponin-reactive autoantibody against the cardiac troponin antigen, wherein assaying comprises(a) contacting the biological sample with a cardiac troponin antigen, under conditions sufficient for binding of the cardiac troponin antigen to any corresponding cardiac troponin-reactive autoantibody present in the sample;
- (b) contacting the biological sample with a labeled cardiac troponin-reactive antibody under conditions sufficient for the labeled cardiac troponin-reactive antibody to compete with said cardiac troponin-reactive autoantibody for specific binding to the cardiac troponin antigen; and
(c) detecting the level of complex(es) comprising the cardiac troponin antigen bound to the labeled cardiac troponin-reactive antibody, wherein the level of said complex(es) is negatively correlated with the level of the corresponding cardiac troponin-reactive autoantibody present in the sample; and
wherein;
detecting an elevated level of cardiac troponin-reactive autoantibody in the biological sample in comparison to the predetermined normal control sample provides indication that the biological sample is scored as one in which the cardiac troponin antigen assay is not reliable, anddetecting a level of cardiac troponin-reactive autoantibody that is not elevated in the biological sample in comparison to the predetermined normal control sample provides indication that the biological sample is scored as one in which the cardiac troponin antigen assay is reliable.
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Abstract
The invention provides among other things methods and kits based on assaying for cardiac troponin autoantibodies, either in conjunction with an assay for cardiac troponin and/or as an independent indicator of cardiac pathology, such as myocarditis, cardiomyopathy, and/or ischemic heart disease. Assay methods of the invention can be employed among other things to identify cardiac pathology, or risk thereof, in subjects who have an autoimmune disease or who are related to an individual with an autoimmune disease. In particular embodiments, the invention also provides a method of determining whether a subject having, or at risk for, a cardiac pathology is a candidate for immunosuppressive therapy or immunoabsorption therapy. The invention also provides kits and kit components that are useful for performing the methods of the invention.
57 Citations
26 Claims
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1. A method of determining the reliability of a cardiac troponin antigen assay in a biological sample from a subject, the method comprising
assaying the biological sample from the subject for an autoantibody reactive with the cardiac troponin antigen being assayed, to allow detection of an elevated level of the cardiac troponin-reactive autoantibody against the cardiac troponin antigen in the biological sample in comparison to a predetermined normal control sample having normal values of cardiac troponin-reactive autoantibody against the cardiac troponin antigen, wherein assaying comprises (a) contacting the biological sample with a cardiac troponin antigen, under conditions sufficient for binding of the cardiac troponin antigen to any corresponding cardiac troponin-reactive autoantibody present in the sample; -
(b) contacting the biological sample with a labeled cardiac troponin-reactive antibody under conditions sufficient for the labeled cardiac troponin-reactive antibody to compete with said cardiac troponin-reactive autoantibody for specific binding to the cardiac troponin antigen; and (c) detecting the level of complex(es) comprising the cardiac troponin antigen bound to the labeled cardiac troponin-reactive antibody, wherein the level of said complex(es) is negatively correlated with the level of the corresponding cardiac troponin-reactive autoantibody present in the sample; and
wherein;detecting an elevated level of cardiac troponin-reactive autoantibody in the biological sample in comparison to the predetermined normal control sample provides indication that the biological sample is scored as one in which the cardiac troponin antigen assay is not reliable, and detecting a level of cardiac troponin-reactive autoantibody that is not elevated in the biological sample in comparison to the predetermined normal control sample provides indication that the biological sample is scored as one in which the cardiac troponin antigen assay is reliable. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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- 17. A test kit for use in assaying a biological sample from a human for an autoantibody reactive with a cardiac troponin antigen, the test kit comprising a humanized monoclonal antibody, wherein the humanized monoclonal antibody is specific for a cardiac Troponin-I or Troponin-T, wherein the test kit additionally comprises a solid phase and a capture agent affixed to the solid phase, wherein the capture agent is selected from the group consisting of a cardiac troponin antigen and a human-specific antibody which binds to the cardiac troponin-reactive autoantibody against the cardiac troponin antigen, and wherein, if the capture agent comprises a cardiac troponin antigen, the kit additionally comprises a human-specific antibody which binds to the cardiac troponin-reactive autoantibody against the cardiac troponin antigen.
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26. A test kit for use in assaying a biological sample from a human for an autoantibody reactive with a cardiac troponin antigen, the test kit comprising a humanized monoclonal antibody, wherein the humanized monoclonal antibody is specific for a cardiac Troponin-I or Troponin T, wherein the test kit additionally comprises a labeled non-human monoclonal antibody, wherein the non-human monoclonal antibody is specific for a cardiac Troponin-I or Troponin-T, and a human-specific antibody which binds to the cardiac troponin-reactive autoantibody against the cardiac troponin antigen.
Specification