Creative Biolabs is a well-recognized expert in the field of antibody generation and production. Especially, we have launched a series of in vitro diagnostic (IVD) antibody development services for different infections and diseases. Scientific progress has resulted in the discovery of novel disease biomarkers to fulfill the need for a quicker, more specific and more accurate diagnosis. Particularly, we provide IVD antibody development services against the troponin marker.

Troponin

Troponin is a component of thin filaments (along with actin and tropomyosin). It is integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Troponin is a complex of three regulatory proteins (troponin C, troponin I, and troponin T). Troponin is found in skeletal muscle and myocardium, but the specific types of troponin differ in different types of muscle. The main difference is that the TnC subunit of troponin has four calcium ion-binding sites in skeletal muscle and only three in the cardiac muscle.

Mutations in cardiac troponin subunits can cause cardiomyopathy, including familial hypertrophic cardiomyopathy. Increased levels of cardiac protein isoforms of troponin circulating in the blood have been shown to be a biomarker of heart disorders, the most important of which is myocardial infarction. The discussion of troponin typically relates to its functional characteristics and/or its usefulness as a diagnostic or therapeutic target for various cardiac diseases, particularly as a highly specific marker of myocardial infarction or heart muscle cell death. Elevated troponin levels also have prognostic importance under many conditions of diagnostic use.

Structure of Troponin. Fig.1 Structure of Troponin. (Das, 2017)

Troponin Marker of Myocardial Infarction

MI implies the process of myocardial cell death by ischemia or the perfusion imbalance between supply and requirement within the coronary arteries resulting in an acute thrombotic process. The early detection of MI is crucial for the establishment of anti-thrombotic therapy to limit myocardial damage and preserve cardiac function. It was widely accepted that troponin is a powerful biomarker for the diagnosis of MI. Meanwhile, high-sensitivity assays for both troponin I and T are available to be used for the early determination of MI. Progresses in immunoassay technology have led to multiple second-generation troponin I assays and a fourth-generation troponin T assay. Besides, troponin-T assays are able to be used in emergency and ambulatory settings, and it is credible above serum level of ≥ 0.10 ng/ml. In addition, except their diagnostic value, cardiac troponins also provide prognostic information as well. Patients with clinical evidence of ischemia and raised troponins have worse outcomes when contrast to those without detectable troponin in the circulation.

Part A shows the troponin release following AMI, part B shows the troponin release following minor myocardial injury. In AMI, troponin raises obviously above the 99th percentile limit (dotted line) within hours of symptom onset and then gradually reduces over several days. Fig. 2 Part A shows the troponin release following AMI, part B shows the troponin release following minor myocardial injury. In AMI, troponin raises obviously above the 99th percentile limit (dotted line) within hours of symptom onset and then gradually reduces over several days. (Melanson, 2007)

Cardiac Troponin (cTn) Marker of Coronary Artery Disease

CAD, also known as coronary vascular, arteriosclerotic and ischemic heart disease, is the major cause of death in the United States. Patients with CAD present a disordered flowing of blood to the heart. When the heart can't get enough blood, symptoms may contain pain or pressure in the chest, arm or jaw. Determination of an increase (fall) in troponin is a crucial part of the current universal identification of myocardial infarction (MI). What's more, troponin is used clinically to discriminate acute coronary syndromes (ACS) into unstable angina and MI. In a research of 5764 older individuals, incidence of cardiovascular disease and coronary heart disease was notably connected with increasing concentrations of troponin I. Another study compared the strength of connection of cTn concentrations with cardiovascular and non-cardiovascular mortality, revealed that higher cTn was observably connected with cardiovascular death rather than noncardiovascular death.

Connection between indexed left ventricular mass and plasma cardiac troponin I concentrations. Similar connection was revealed in patients with coronary artery disease. Fig. 3 Connection between indexed left ventricular mass and plasma cardiac troponin I concentrations. Similar connection was revealed in patients with coronary artery disease. (Chin, 2014)

cTnT Marker of Heart Disorders

Cardiac troponin T (cTnT) and troponin I (cTnI) are cardiac regulatory proteins which manage the interaction between actin and myosin mediated by calcium. The cardiac forms of these proteins are produced by particular genes and have the possibility of being exclusive to the myocardium. cTnT is expressed to a small extent in skeletal muscle, however, cTnI has been discovered only in the myocardium. Importantly, the determination of serum cTnT and cTnI is better than that of cardiac muscle enzyme measurements due to their outstanding sensitivity and specificity in the authentication of cardiac muscle damage.

Besides, for patients with acute coronary syndromes, diagnostic elevations of troponin always have prognostic and therapeutic significance. The raised levels of cTnT or cTnI of acute coronary syndromes patients are an adverse prognostic indicator. In addition, troponin is the biomarker for identifying cardiac injury in patients with renal failure, such as those with end-stage renal disease (ESRD) having long-term dialysis.

Troponin Marker of Sepsis Infections

Elevation of cardiac troponins and creatinine kinase is frequently observed in setting of systemic inflammatory response syndrome (SIRS), sepsis, or septic shock. Troponin elevation in setting of sepsis has been proposed as a biomarker for underlying myocardial dysfunction.

In the case of sepsis, the metabolic needs of the heart are high, and in order to meet these requirements, it is necessary to increase the coronary blood flow. There are two storage forms of cardiac troponins: cytosolic and myofibril. The quantity of troponins in cytosol is 35 times lower than in myofibril. It has been hypothesized that in a setting of stress, cytosolic troponins may leak and lead to a rise in blood levels even in the absence of any damage to myofibril. This hypothesis could partially explain septic shock related troponin elevations (SRTE) as there is evidence of myofibril ischemic damage in setting of sepsis.

IVD Antibody Development Services Targeting Troponin Marker

Antibodies are core elements for antibody-based immunoassays for detecting and quantifying antigens of interest in all kinds of samples such as the serum, urine, tissue preparations, and so on. IVD antibodies are extensively used for disease screening, prognosis, and therapeutic monitoring. With our versatile IVD platform, Creative Biolabs is proud to develop novel anti-troponin antibody from scratch to commercial IVD kit (we can also start with provided antibody candidates). If you are interested in our services, please do not hesitate to contact us for more details.

References

  1. Das, Biswajit., (2017). “Cardiac troponins: Current status.” J Am Coll 7(1): 1-5.
  2. Melanson, S. E. (2007). “Cardiac Troponin Assays A View From the Clinical Chemistry Laboratory.” Circulation 116(18), e501-e504.
  3. Chin, C. W. (2014). “High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis.” European heart journal ehu189.

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