The following is a summary of “Semaphorin 7A promotes endothelial permeability and inflammation via plexin C1 and integrin β1 in Kawasaki disease,” published in the April 2024 issue of Pediatrics by Huang et al.

Kawasaki disease (KD) is a significant challenge in pediatric medicine due to its systemic vasculitis and endothelial dysfunction. While the role of Semaphorin 7A (Sema7A) has been noted in cardiovascular diseases, its implications in KD have remained elusive. This study endeavors to unravel the impact of Sema7A on endothelial permeability and the inflammatory response within the context of KD.

To discern these intricate mechanisms, serum samples were collected from 68 patients with KD alongside 25 healthy children (HC) for comparison. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) levels in serum, while flow cytometry analyzed Sema7A expression in blood cells. Additionally, ex vivo monocytes were utilized for Sema7A shedding assays. In vitro experiments involving human coronary artery endothelial cells (HCAECs) cultured in KD sera were conducted to elucidate the impact of Sema7A. These experiments assessed the levels of proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-18 using ELISA and qRT-PCR, as well as the permeability of HCAEC monolayers measured via FITC-dextran assays.

The findings revealed a significant elevation of serum Sema7A levels in patients with KD compared to HC, correlating with disease severity. Monocytes were identified as a source of heightened serum Sema7A, suggesting an ADAM17-dependent shedding process. Furthermore, sera from patients with KD induced the upregulation of plexin C1 and integrin β1 in HCAECs relative to HC sera. Sema7A was found to mediate proinflammatory cytokine production in HCAECs through an integrin β1-dependent pathway, while both plexin C1 and integrin β1 contributed to Sema7A-induced HCAEC hyperpermeability.

In conclusion, Sema7A emerges as a key player in the pathogenesis of KD vasculitis, exacerbating endothelial permeability and inflammation via a pathway reliant on plexin C1 and integrin β1. These findings position Sema7A as a potential biomarker and therapeutic target in the management and prognosis of KD, offering new avenues for intervention in this challenging pediatric condition.

Source: bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-04766-3