medical director Pediatrics Chiba-shi, Chiba, Japan
[BACKGROUND/AIM] KD is known to be associated with an aberrant immune response and abnormal platelet activation, however its etiology is still largely unknown. Myosin light chain 9 (Myl9), a ligand for CD69 expressed by inflammatory leukocytes, is released by activated platelets and form net-like structures named “Myl9 nets” inside blood vessels at inflammatory sites. Myl9 has been reported to involve in the airway inflammation and inflammatory bowel disease. The mechanism of inflammation induction is called the “CD69-Myl9 system” in which Myl9 nets likely act as a platform for the recruitment and maintenance of CD69-expressing inflammatory cells in inflamed tissues, thereby exacerbating the inflammation. We set up the hypothesis that CD69-Myl9 system can be involved in the onset of KD vasculitis. [METHODS] 1) We observed the expression of Myl9 in the coronary arteries of 6 patients. 3 KD patients died from myocardial infarction and 3 controls died from external causes. 2) We measured plasma Myl9 levels of 76 KD cases, 16 cases of febrile controls including cases who were required differentiation from KD, and 17 cases of healthy controls. 3) We stimulated platelets from 9 KD patients and 5 healthy controls with thrombin in vitro, and measured the levels of Myl9 released from platelets before and after stimulation. [RESULTS] 1) The highest Myl9 expression was observed in thrombi during the acute phase and in the intima and adventitia of coronary arteries during the chronic phase in the coronary aneurysm of KD patients. 2) Plasma Myl9 levels were significantly higher in the acute phase KD patients than patients with other febrile illnesses (p=0.016), and decreased during the recovery phase (p < 0.001). All 4 cases with plasma Myl9 levels higher than 1000ng/mL caused complication of moderate or giant coronary artery aneurysm. 3) In vitro, platelets from healthy controls released Myl9 upon thrombin stimulation significantly, whereas platelets from KD patients released Myl9 independently of thrombin stimulation. [CONCLUSION] Myl9 expression is significantly increased during KD vasculitis. Myl9 levels may be a useful biomarker to estimate inflammation and IVIG responsiveness to KD.
