Exploring exosome-related genes as candidate biomarkers in primary immune thrombocytopenia through transcriptomics...

Primary Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia and bleeding tendency. Exosomes mediate abnormal crosstalk between immune cells and megakaryocytes in ITP, suggesting that exosome-related genes may serve as potential candidates for understanding disease pathogenesis. ITP transcriptome data and exosome-related genes (ERGs) were retrieved from public databases. Potential candidate genes were preliminarily identified by intersecting ITP's differentially expressed genes (DEGs) with exosome-related key module genes, followed by exploratory screening via machine learning and the construction of a preliminary predictive model. Multi-dimensional analyses (enrichment, immune infiltration [subsequently removed due to methodological concerns], drug prediction) and RT-qPCR validation were performed. Four candidate genes (GABARAPL1, SLC39A14, HIBADH, GSR) were identified through bioinformatic analysis, involved in spliceosome and other pathways (P < 0.05, |NES| > 1). GABARAPL1, SLC39A14, and HIBADH showed exploratory correlations with specific functional T-cell subsets (|cor| > 0.3, P < 0.05). Molecular docking simulations suggested potential binding feasibility between SLC39A14/nortriptyline and GSR/oxiglutatione (binding free energy < -5 kcal/mol). RT-qPCR confirmed the significant downregulation of GABARAPL1, SLC39A14, and GSR in ITP patients (P < 0.05), while HIBADH did not show statistically significant changes (P > 0.05). In this exploratory study, GABARAPL1, SLC39A14, and GSR were identified as potential candidate biomarkers with experimental support from clinical samples. HIBADH, while predicted by bioinformatic analysis, requires further investigation to determine its clinical relevance. These findings provide exploratory insights and a preliminary basis for future hypothesis-driven research on the role of exosome-related genes in ITP.