20.500.12556/DiRROS-29731 Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers Introduction: Immunoglobulin A vasculitis (IgAV) in adults has a variable disease course, with patients often developing gastrointestinal and renal involvement and thus contributing to higher mortality. Due to understudied molecular mechanisms in IgAV currently used biomarkers for IgAV visceral involvement are largely lacking. Our aim was to search for potential serum biomarkers based on the skin transcriptomic signature. Methods: RNA sequencing analysis was conducted on skin biopsies collected from 6 treatment-naïve patients (3 skin only and 3 renal involvement) and 3 healthy controls (HC) to get insight into deregulated processes at the transcriptomic level. 15 analytes were selected and measured based on the transcriptome analysis (adiponectin, lipopolysaccharide binding protein (LBP), matrix metalloproteinase-1 (MMP1), C-C motif chemokine ligand (CCL) 19, kallikrein-5, CCL3, leptin, C-X-C motif chemokine ligand (CXCL) 5, osteopontin, interleukin (IL)-15, CXCL10, angiopoietin-like 4 (ANGPTL4), SERPIN A12/vaspin, IL-18 and fatty acid-binding protein 4 (FABP4)) in sera of 59 IgAV and 22 HC. Machine learning was used to assess the ability of the analytes to predict IgAV and its organ involvement. Results: Based on the gene expression levels in the skin, we were able to differentiate between IgAV patients and HC using principal component analysis (PCA) and a sample-to-sample distance matrix. Differential expression analysis revealed 49 differentially expressed genes (DEGs) in all IgAV patient's vs. HC. Patients with renal involvement had more DEGs than patients with skin involvement only (507 vs. 46 DEGs) as compared to HC, suggesting different skin signatures. Major dysregulated processes in patients with renal involvement were lipid metabolism, acute inflammatory response, and extracellular matrix (ECM)-related processes. 11 of 15 analytes selected based on affected processes in IgAV skin (osteopontin, LBP, ANGPTL4, IL-15, FABP4, CCL19, kallikrein-5, CCL3, leptin, IL-18 and MMP1) were significantly higher (p-adj < 0.05) in IgAV serum as compared to HC. Prediction models utilizing measured analytes showed high potential for predicting adult IgAV. Conclusion: Skin transcriptomic data revealed deregulations in lipid metabolism and acute inflammatory response, reflected also in serum analyte measurements. LBP, among others, could serve as a potential biomarker of renal complications, while adiponectin and CXCL10 could indicate gastrointestinal involvement. acute inflammatory response adults IgA vasculitis lipid metabolism machine learning RNA sequencing serum biomarkers akutni vnetni odziv odrasli IgA vaskulitis metabolizem lipidov strojno učenje sekvenciranje RNA serumski biološki označevalci true false true Angleški jezik Slovenski jezik Neznano 2026-06-04 09:41:08 2026-06-04 09:41:08 2026-06-05 04:05:55 0000-00-00 00:00:00 2024 0 0 Nasl z nasl. zaslona; Opis vira z dne 18. 6. 2024; str. 1-12 iss. 1, [article no.] 85 Vol. 26 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-002 1478-6362 10.1186/s13075-024-03317-6 199720707 RAZ_Bajzelj_Matija_2024.pdf RAZ_Bajzelj_Matija_2024.pdf 1 7810033380A278D8DE4DA30D2142CDAB 699854a865a3f3094c778a23bb1a063dafcf58a23ab331a1996131ddcf9319e7 f5f74cd8-5fe8-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44677 https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-024-03317-6 1 c2fe861f-5fe8-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44676 Univerzitetni klinični center Ljubljana 0 0 0