Plasma Proteomic Analysis Reveals the Potential Role of Lectin and Alternative Complement Pathways in IgA Vasculitis Pathogenesis

Abstract

Background: IgA vasculitis (IgAV) is the most common form of childhood vasculitis. A better understanding of its pathophysiology is required to identify new potential biomarkers and treatment targets. Objective: to assess the underlying molecular mechanisms in the pathogenesis of IgAV using an untargeted proteomics approach. Methods: Thirty-seven IgAV patients and five healthy controls were enrolled. Plasma samples were collected on the day of diagnosis before any treatment was initiated. We used nano-liquid chromatography–tandem mass spectrometry (nLC–MS/MS) to investigate the alterations in plasma proteomic profiles. For the bioinformatics analyses, databases including Uniprot, PANTHER, KEGG, Reactome, Cytoscape, and IntAct were used. Results: Among the 418 proteins identified in the nLC–MS/MS analysis, 20 had significantly different expressions in IgAV patients. Among them, 15 were upregulated and 5 were downregulated. According to the KEGG pathway and function classification analysis, complement and coagulation cascades were the most enriched pathways. GO analyses showed that the differentially expressed proteins were mainly involved in defense/immunity proteins and the metabolite interconversion enzyme family. We also investigated molecular interactions in the identified 20 proteins of IgAV patients. We extracted 493 interactions from the IntAct database for the 20 proteins and used Cytoscape for the network analyses. Conclusion: Our results clearly suggest the role of the lectin and alternate complement pathways in IgAV. The proteins defined in the pathways of cell adhesion may serve as biomarkers. Further functional studies may lead the way to better understanding of the disease and new therapeutic options for IgAV treatment.

Keywords

• Henoch–Schönlein purpura
• IgA vasculitis
• pathogenesis
• proteomic
• lectin complement pathway
• alternative complement pathway