The Role Of IDO/TTS-Mediated Tryptophan Metabolism Pathway In Kawasaki Disease

Part Ⅰ Clinical Analysis of 48 cases of Kawasaki diseaseObjective: To understand the clinical features of Kawasaki disease by summarizing up the clinical and laboratory data of 48 cases of Kawasaki disease in acute phase.Methods: The clinical medical records of 48 children with Kawasaki disease in acute phase who were hospitalized in the pediatrics of the Affiliated Hospital of North Sichuan Medical College from October 2017 to December 2018 were collected and analyzed.Results: 1.Among the 48 cases of Kawasaki disease,the proportion of children under 3 years old was higher(83.34%),increased incidience in spring and summer(77.09%)and males were predominant(male and female ratio 1.09:1).2.The cervical lymphadenopathy was less frequently encountered(33.33%)than other principal symptoms during the acute phase.3.There were 21 cases(43.75%)with coronary artery aneurysms(CAAs)in 48 children with Kawasaki disease.The age of younger than 1 year old and pleomorphic rash were higher in CAAs group(p<0.05).4.The serum lactate dehydrogenase(LDH)and lactic acid(Lact)levels were higher in non-coronary artery aneurysms group(NCAAs)(p<0.05).Conclusion: Kawasaki disease occurs mostly in children under 3 years of age 、 males and the season of spring and summer.The cervical lymphadenopathy is less frequently encountered than other principal symptoms during the acute phase.The age of less than 1 year old and the appearance of pleomorphic rash are higher in CAAs,while the levels of serum lactate dehydrogenase(LDH)and lactic acid(Lact)are higher in NCAAs.Part Ⅱ The changes of indoleamine2,3-dioxygenase activity and tryptophanyl-t RNA synthetase level in the plasma of children with Kawasaki diseaseObjective: To study the changes of indoleamine 2,3 dioxygenase(IDO)activity and tryptophanyl-t RNA synthetase(TTS)level in the plasma of children with Kawasaki disease before and after treatment in acute phase and its relationship with Kawasaki disease coronary aneurysms.Methods: A total of 48 Kawasaki disease children in acute phase who were hospitalized in the pediatrics of the Affiliated Hospital of North Sichuan Medical College from October 2017 to December 2018 were enrolled.In the control group,45 children with Henoch-schonlein purpura,45 children with mild pneumonia and 47 normal children who were hospitalized during the same period were enrolled.The content of TTS in plasma was detected by competitive enzyme-linked immunosorbent assay(ELISA).The concentration of tryptophan and kynurenine in plasma was detected by high performance liquid chromatography(HPLC).The activity of IDO was expressed by Kyn/Trp ratio.Level changes before and after Kawasaki disease treatment and in each control group,and whether there were differences in TTS concentration and Kyn/Trp ratio between Kawasaki disease coronary artery aneurysms and non-coronary artery aneurysms group.Results: 1.The IDO activity of Kawasaki disease was significantly increased before treatment(0.044±0.023 vs 0.017±0.006,p<0.05),and the IDO activity decreased significantly after treatment(0.020±0.013 vs 0.044±0.023,p<0.05).2.There was no significant change in TTS concentration before treatment in the acute phase of Kawasaki disease [9.11(0.11,43.07)ng/ml vs 5.22(0.11,31.55)ng/ml,p>0.05],and the TTS concentration after treatment was higher than normal control and before treatment [9.23(0.75,54.14)ng/ml vs 9.11(0.11,43.07)ng/ml,9.23(0.75,54.14)ng/ml vs 5.22(0.11,31.55)ng/ml,p<0.05];3.The IDO activity of the mild pneumonia group was increased(0.027±0.011 vs 0.017±0.006,p<0.05),and the IDO activity of the Henoch-schonlein purpura group was significantly decreased(0.011±0.005 vs 0.017±0.006,p<0.05);The TTS concentration in the acute phase of Henoch-schonlein purpura and mild pneumonia were significantly increased [13.45(3.20,50.85)ng / ml vs 5.22(0.11,31.55)ng / ml,36.20(11.27,77.90)ng / ml vs 5.22(0.11,31.55)ng/ml,p<0.05];5.IDO activity and TTS concentration were not significantly different between CAAs group and NCAAs group(p>0.05).Conclusion: 1.There is abnormal metabolism of tryptophan in the acute phase of Kawasaki disease,and the IDO/TTS-mediated tryptophan metabolism pathway is involved in the pathogenesis of Kawasaki disease.2.The changes of IDO activity and TTS level are not associated with Kawasaki disease coronary artery aneurysms.3.IDO activity decreased and TTS increased significantly in the acute phase of Henoch-schonlein purpura,contrary to the acute phase change of Kawasaki disease,indicating that the IDO/TTS pathway plays different roles in the pathogenesis of them.