Biomarkers for Kawasaki Disease: Clinical Utility and the Challenges Ahead

Abstract

Kawasaki disease (KD) has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the developed world and is increasingly being recognized from several developing countries. It is a systemic vasculitis with a predilection for coronary arteries. The diagnosis is based on a constellation of clinical findings that appear in a temporal sequence. Quite understandably, this can become a problem in situations wherein the clinical features are not typical. In such situations, it can be very difficult, if not impossible, to arrive at a diagnosis. Several biomarkers have been recognized in children with acute KD but none of these has reasonably high sensitivity and specificity in predicting the course of the illness. A line up of inflammatory, proteomic, gene expression and micro-RNA based biomarkers has been studied in association with KD. The commonly used inflammatory markers e.g. erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and total leucocyte counts (TLC) lack specificity for KD. Proteomic studies are based on the identification of specific proteins in serum, plasma and urine by gel electrophoresis. A host of genetic studies have identified genes associated with KD and some of these genes can predict the course and coronary outcomes in the affected individuals. Most of these tests are in the early stages of their development and some of these can predict the course, propensity to develop coronary artery sequelae, intravenous immunoglobulin (IVIg) resistance and the severity of the illness in a patient. Development of clinical criteria based on these tests will improve our diagnostic acumen and aid in early identification and prevention of cardiovascular complications.

How useful are Kawasaki disease risk scoring systems to the Turkish population?

“…Myocardial involvement in acute KD is universal from histologic and functional perspectives; hence, the role of NT-proBNP as a potential biomarker has been extensively studied ( 25 , 26 ). Kim et al ( 27 ) described cardiac troponin I (cTnI) in relation to KD and showed a significant increase in cTnI level in the acute stage of KD.…”

“…This increase was statistically significant in CAL patients. Although some studies have recognized both thrombocytopenia and significant thrombocytosis as predictors of CAAs or IVIG resistance ( 25 , 38 ), another study showed no association ( 24 ). The exact mechanism underlying thrombocytosis is unclear.…”

“…The exact mechanism underlying thrombocytosis is unclear. It has been suggested that elevated thrombopoietin level caused by acute inflammatory responses can lead to thrombocytopoiesis ( 25 , 38 ).…”

Elevated Levels of Pentraxin 3 Correlate With Neutrophilia and Coronary Artery Dilation During Acute Kawasaki Disease

“…Previous studies have focused on cytokines and chemokines during acute KD. However, these proteins are relatively non-specific and are elevated in many inflammatory processes ( 21 , 22 ).…”

Cardiovascular Involvement in Kawasaki Disease Is Much More Than Mere Coronary Arteritis

“…It has been reported to be positively correlated with impairment of ventricular relaxation in patients with KD (27). Gamma-glutamyl transferase and alanine transferase, however, have not been found to be useful in establishing a clinical diagnosis of KD (40).…”