Up-regulated vitronectin in Kawasaki disease shock syndrome serves as a potential biomarker.

Abstract

Background: Kawasaki disease shock syndrome (KDSS) pathogenesis involves an immune inflammatory response related to Kawasaki disease (KD) that damages microvessel endothelial cells, leading to microcirculatory disorders. Its clinical manifestations are characterized by hypotension, poor peripheral perfusion, and a high risk of coronary artery lesions (CALs). Currently, there are few reports on biomarkers based on endothelial cell dysfunction in KDSS. This study aims to identify potential biomarkers of endothelial dysfunction in KDSS at the protein level.

Methods: In this study, we recruited age- and sex-matched participants, consisting of KDSS patients, KD patients, and healthy control (HC) children. The inflammatory indicators and cytokines were compared between the KD and KDSS groups. The endothelial barrier function was assessed by dynamically measuring the cell impedance in human coronary artery endothelial cells (HCAECs). Tandem mass tag (TMT)-based proteomics was used to profile the differentially expressed proteins (DEPs) in KDSS plasma. Function and pathway enrichment analyses were performed for related pathways involved in KDSS pathology. Key proteins were validated through Western blotting.

Results: Inflammatory cytokines were significantly higher in the KDSS group than in the KD group, and included interleukin-6 (IL-6) (259.37±385.20 vs. 32.96±22.84 pg/mL, P=0.02); soluble interleukin-2 receptor (sIL-2R) (2,529.78±2,016.38 vs. 1,250.50±359.76 pg/mL, P=0.01); and interleukin-10 (IL-10) (63.20±49.91 vs. 12.85±9.47 pg/mL, P=0.005). The KDSS plasma treatment led to earlier and more severe barrier dysfunction in the HCAECs than that seen with the KD plasma treatment. Among the 455 plasma proteins analyzed, 58 were up-regulated and 52 were down-regulated in the KDSS patients. Moreover, 13 DEPs were identified as potential key proteins, and these DEPs primarily associated with cell activation signaling, inflammatory cascades, and endopeptidase activity regulation. Vitronectin was validated to be up-regulated in the KDSS patients.

Conclusions: This study provides a potential plasma proteomic profile for KDSS. Vitronectin may serve as a pathogenesis-based diagnostic biomarker for KDSS.