Ingenuity pathway analysis of biomarkers and immune mediators of Kawasaki disease

Abstract

Kawasaki Disease (KD) is an acute systemic vasculitis of unknown etiology primarily affecting children younger than five. As the etiology of KD remains unknown, diagnosis relies on a trained clinician identifying the sequential appearance of a constellation of clinical signs, and treatment consists of non-specific suppression of inflammation. A multitude of biomarkers associated with acute KD have been studied to understand the underlying mechanisms that may lead to a distinguishable diagnosis. Ingenuity Pathway Analysis (IPA) software is an essential tool for visualizing canonical pathways, upstream and downstream regulators and signaling networks. This study employed IPA to analyze the protein expression profiles of select markers for inflammation, tissue degradation, and vascular remodeling in clinically characterized KD patient serum samples to understand the pathophysiological pathways in acute KD, the development of coronary artery abnormalities (CAA) in KD patients, and intravenous immunoglobulin (IVIG) treatment response. While studies have highlighted the identification of potential biomarkers related to the immune response behind KD, subgroup analyses associated with KD publicly available within the IPA platform did not include all three clinical phases of KD, the acute, subacute and convalescent, and did not include analyses based on the presence or absence of CAA. Comparative analysis not only between the clinical phases of KD, but also between various clinical outcomes in KD patients (i.e., presentation of CAA and IVIG resistance), will allow for a better understanding of KD immunopathogenesis, identify prognostic biomarkers for diagnosis of acute KD and risks of CAA formation, and differentiate between IVIG resistant and responsive patients.