P2.031: Plasma Exosomal-Derived SERPINA1 and GNAI2 Downregulation as Potential Diagnostic Biomarkers of Kawasaki Disease with Coronary Artery Aneurysms

Background: Kawasaki Disease (KD) with coronary artery aneurysms (CAAs) is currently the primary cause of childhood acquired heart disease with unclear pathogenesis. The aim of this study was to explore the exosomal candidate proteins for identifying KD with CAAs in early stage.

Methods: We employed mass spectrometry to quantify the exosomal protein expression profiles in patients with KD compared with healthy controls and febrile controls. Total 60 subjects were included, with 40 subjects in 5 groups for bioinformatics analyses (n = 8 in each group) and 20 subjects in 5 groups for verification (n = 4 in each group). The KD patients were further stratified into groups of KD without CAAs, KD with small and medium CAAs, and KD with giant CAAs. To elucidate the functional roles of the differentially expressed proteins (DEPs), we conducted comprehensive bioinformatics analyses. Additionally, Western blotting (WB) was performed to validate the expression levels of selected DEPs.

Results: Total 104 DEPs were expressed in KD patients compared with healthy controls and febrile controls. Trend analysis of thses DEPs revealed 54 significantly changed DEPs associated with increased disease severity. SERPINA1 and GNAI2 were selected from the complement related and G-protein related pathways respectively among those DEPs above, and they were significantly decreased in KD patients with CAAs compared with those without CAAs by WB verification. Besides, bioinformatics analysis revealed the DEPs and related pathways in KD without CAAs and KD with CAAs groups separately. There were 91 DEPs specific to KD patients with CAAs, associated with neutrophil extracellular trap information and complement related pathways, while 16 DEPs specifically expressed in those without CAAs, associated with viral infection and immunity pathways. Additionally, for DEPs among different severity of CAAs, 102 DEPs were specific to KD patients with small and medium CAAs, associated with complement related pathways and platelet activation pathways, whereas 34 DEPs were specific to those with giant CAAs, associated with cell function pathways.

Conclusion: In conclusion, this study provides plasmatic exosomal protein profiles in KD patients with CAAs, suggesting that SERPINA1 and GNIA2 might serve as novel potential diagnostic biomarkers for KD with CAAs.