Tohoku J. Exp. Med., 2015 October, 237(2)

Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease

YUUKI KONNO,¹ IKUKO TAKAHASHI,¹ AYUKO NARITA,² OSAMU TAKEDA,³ HIROMI KOIZUMI,³ MASAMICHI TAMURA,⁴ WATARU KIKUCHI,⁵ AKIRA KOMATSU,⁶ HIROAKI TAMURA,¹ SATOKO TSUCHIDA,¹ ATSUKO NOGUCHI¹ and TSUTOMU TAKAHASHI¹

¹Department of Pediatrics, Akita University Graduate School of Medicine, Akita, Akita, Japan
²Division of Pediatrics, Yamamoto General Hospital, Noshiro, Akita, Japan
³Division of Pediatrics, Akita Municipal General Hospital, Akita, Akita, Japan
⁴Division of Pediatrics, Akita Red-Cross Hospital, Akita, Akita, Japan
⁵Division of Pediatrics, Ogachi Central Hospital, Yuzawa, Akita, Japan
⁶Division of Pediatrics, Yokote Municipal Hospital, Yokote, Akita, Japan

Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD.

keywords —— acid sphingomyelinase; ceramide; C-reactive protein; Kawasaki disease; sphingolipid metabolism

© 2015 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2015, 237, 133-140

Correspondence: Tsutomu Takahashi, M.D., Department of Pediatrics, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita 010-8543, Japan.

e-mail: tomy@med.akita-u.ac.jp