CD36 is Associated With the Development of Coronary Artery Lesions in Patients With Kawasaki Disease.

Mindy Ming-Huey Guo,Ying-Hsien Huang,Feng-Sheng Wang,Ho-Chang Kuo,Ling-Sai Chang,Kuang-Den Chen

doi:10.3389/fimmu.2022.790095

Abstract

Kawasaki disease (KD) is an autoimmune-like vasculitis of childhood involving the coronary arteries. Macrophages require scavenger receptors such as CD36 to effectively clear cellular debris and induce self-tolerance. In this study, we hypothesized that CD36 plays an important role in the immunopathogenesis of KD, by aiding in the clearance of plasma mitochondrial DNA, and by amplifying the immune response by activating the inflammasome pathway via AIM2. Fifty-two healthy controls, 52 febrile controls, and 102 KD patients were recruited for RT-PCR of target mRNA expression and plasma mitochondrial DNA. Blood samples were obtained 24 hours prior and 21 days after the administration of intravenous immunoglobulin (IVIG) therapy. Patients with acute KD had higher plasma levels of cell-free mitochondrial DNA (ND1, ND4, and COX1), and higher mRNA expressions of CD36 and AIM2 when compared to both healthy and febrile controls. A greater decrease in both CD36 and AIM2 mRNA expression after IVIG therapy was associated with the development of coronary artery lesions. Coronary artery lesions were associated with a larger decrease of CD36 expression following IVIG therapy, which may indicate that prolonged expression of the scavenger receptor may have a protective effect against the development of coronary artery lesions in KD.

Highlights

Kawasaki disease (KD) is the most common cause of acquired heart disease during childhood, especially in Asian countries like Japan and Taiwan [1, 2]
We found that patients with acute Kawasaki disease had statistically significant higher levels of ND1, ND4, and COX1 mitochondrial DNA when compared to healthy controls and febrile controls (Figure 1)
We found that KD patients who developed coronary artery lesions had a greater decrease in AIM2 mRNA expression after intravenous immunoglobulin (IVIG) therapy, changes in AIM2 mRNA expression were not associated with IVIG resistance (Figures 4B, C)

Summary

Introduction

Kawasaki disease (KD) is the most common cause of acquired heart disease during childhood, especially in Asian countries like Japan and Taiwan [1, 2]. Activated macrophages are critical to the development of coronary artery lesions in KD and produce such inflammatory cytokines as tumor necrosis factor-a and vascular endothelial growth factor, both of which further amplify the inflammatory response. They produce proteases, including matrix metalloproteinase-2 (MMP-2) and MMP-9, which degrade the elastin fibers within the arterial wall, leading to coronary artery dilatation and aneurysms [5]. CD36, a M2 marker, has been extensively linked to the development of vascular disease and was found to have increased mRNA expression during the acute phase of KD, but decreased after IVIG therapy [10]

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Conclusion