Proteomic analysis of urine reveals biomarkers for identification of kidney injury in children's abdominal-type Henoch-Schönlein purpura

BackgroundAbdominal Henoch - Schönlein purpura (AHSP), being the most prevalent form of Henoch - Schönlein purpura, has a significant impact on the short - term prognosis of the disease and often involves the kidneys, leading to renal complications that affect children's long - term prognosis. However, the existing early assessment criteria for AHSP and its renal complications are inadequate. The urinary proteome may offer valuable insights.ObjectiveTo confirm the significance of urinary proteomics in the early detection of AHSP and its renal complications in children.MethodsThe urinary proteome of AHSP patients (with and without renal involvement) was compared with that of healthy controls using liquid chromatography - tandem mass spectrometry (LC - MS/MS) in data - independent acquisition (DIA) mode. Differentially expressed proteins were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Mfuzz was employed to analyze the expression levels of proteins related to disease onset and progression. The STRING database was used for protein - protein interaction analysis of relevant biological pathways. Selected differential proteins were verified using parallel reaction monitoring (PRM).ResultsA total of 441 dysregulated differentially expressed proteins (DEPs) were associated with the pathogenesis of AHSP, mainly related to cell adhesion, signal transduction or regulation, and reactions or pathways mediated by inflammatory cells or factors, and predominantly enriched in the lysosomal pathway. A total of 275 DEPs related to renal complications of AHSP were mainly associated with immune processes mediated by immunoglobulins, predominantly enriched in the regulatory pathways of the actin cytoskeleton. Time series clustering analysis identified 10 discrete clusters; three upregulated and two downregulated clusters were chosen to form respective panels. These panels involved various biological processes such as immune and inflammatory processes, lipid metabolism, glycosylation, coagulation, oxidative detoxification processes, and the Wnt signaling pathway, with several important biological pathways being enriched. Protein - protein interaction analysis of key pathways revealed three distinct MCODE networks, mainly involving proteins related to immunity, coagulation, collagen, and integrins. In the validation phase, at least eight urinary proteins useful for diagnosing AHSP or its renal complications were identified, demonstrating good diagnostic performance.ConclusionThis study offers novel perspectives on the pathogenesis of AHSP and its renal complications in children, and the related proteins may serve as potential biomarkers for diagnosing AHSP and identifying the onset of renal damage. The findings of this study emphasize the importance of urinary proteomics in understanding the disease mechanisms and provide a basis for further research on early diagnosis and treatment.