Abstract：Objective To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD. Methods In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics. Results A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins. Conclusions The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.
ZHANG Fan,ZHANG Qian-Wen,WANG Na-Na et al. Proteomics of serum exosomes in children in the acute stage of Kawasaki disease: a prospective study[J]. CJCP, 2022, 24(4): 392-398.
McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association[J]. Circulation, 2017, 135(17): e927-e999. PMID: 28356445. DOI: 10.1161/CIR.0000000000000484.
Tang Y, Yan W, Sun L, et al. Coronary artery aneurysm regression after Kawasaki disease and associated risk factors: a 3-year follow-up study in East China[J]. Clin Rheumatol, 2018, 37(7): 1945-1951. PMID: 29330741. DOI: 10.1007/s10067-018-3977-6.
Qiu H, He Y, Rong X, et al. Delayed intravenous immunoglobulin treatment increased the risk of coronary artery lesions in children with Kawasaki disease at different status[J]. Postgrad Med, 2018, 130(4): 442-447. PMID: 29745742. DOI: 10.1080/00325481.2018.1468712.
Zhang L, Song QF, Jin JJ, et al. Differential protein analysis of serum exosomes post-intravenous immunoglobulin therapy in patients with Kawasaki disease[J]. Cardiol Young, 2017, 27(9): 1786-1796. PMID: 28803590. DOI: 10.1017/S1047951117001433.
Hanjani NA, Esmaelizad N, Zanganeh S, et al. Emerging role of exosomes as biomarkers in cancer treatment and diagnosis[J]. Crit Rev Oncol Hematol, 2022, 169: 103565. PMID: 34871719. DOI: 10.1016/j.critrevonc.2021.103565.
de Vries JJ, Snoek CJM, Rijken DC, et al. Effects of post-translational modifications of fibrinogen on clot formation, clot structure, and fibrinolysis: a systematic review[J]. Arterioscler Thromb Vasc Biol, 2020, 40(3): 554-569. PMID: 31914791. PMCID: PMC7043730. DOI: 10.1161/ATVBAHA.119.313626.
Li D, Chen X, Li X, et al. Effectiveness and safety of dual antiplatelet therapy in coronary aneurysms caused by Kawasaki disease in children: study protocol for a multicenter randomized clinical trial[J]. Transl Pediatr, 2021, 10(7): 1914-1923. PMID: 34430440. PMCID: PMC8349963. DOI: 10.21037/tp-21-74.
Jin J, Wang J, Lu Y, et al. Platelet-derived microparticles: a new index of monitoring platelet activation and inflammation in Kawasaki disease[J]. Indian J Pediatr, 2019, 86(3): 250-255. PMID: 30159809. DOI: 10.1007/s12098-018-2765-2.
van Schaarenburg RA, Suurmond J, Habets KL, et al. The production and secretion of complement component C1q by human mast cells[J]. Mol Immunol, 2016, 78: 164-170. PMID: 27648858. DOI: 10.1016/j.molimm.2016.09.001.
van de Bovenkamp FS, Dijkstra DJ, van Kooten C, et al. Circulating C1q levels in health and disease, more than just a biomarker[J]. Mol Immunol, 2021, 140: 206-216. PMID: 34735869. DOI: 10.1016/j.molimm.2021.10.010.
Hester CG, Frank MM. Complement activation by IgG containing immune complexes regulates the interaction of C1q with its ligands[J]. Mol Immunol, 2019, 116: 117-130. PMID: 31634815. DOI: 10.1016/j.molimm.2019.10.004.
Al-Damry NT, Attia HA, Al-Rasheed NM, et al. Sitagliptin attenuates myocardial apoptosis via activating LKB-1/AMPK/Akt pathway and suppressing the activity of GSK-3β and p38α/MAPK in a rat model of diabetic cardiomyopathy[J]. Biomed Pharmacother, 2018, 107: 347-358. PMID: 30099338. DOI: 10.1016/j.biopha.2018.07.126.
