POS1438 ANALYSIS OF THE PLASMA PROTEOME PROVIDES MECHANISTIC INSIGHTS INTO THE PATHOPHYSIOLOGY OF ANCA-ASSOCIATED VASCULITIS

Background The pathogenesis of ANCA-associated vasculitis (AAV) remains largely unknown. Proteinase 3 (PR3)- and myeloperoxidase (MPO)-AAV are two cateogories AAV with distinct genetic background, but mechanistic differences between the poorly characterized. We hypothesized that in-depth studies plasma proteome in patients active would provide clues to molecular cellular mechanisms behind these disorders. Objectives To improve our understanding disease pathophysiological PR3- MPO-AAV. Methods Plasma samples were collected at six Swedish rheumatological and/or nephrological centers from 42 PR3-AAV- 25 MPO-AAV prior commencement therapy 138 healthy matched controls. All classified into granulomatosis polyangiitis or microscopic according European Medicines Agency algorithm. Samples analysed for relative levels 181 proteins associated inflammation cardiovascular disease, using proximity extension assay (OLINK Proteomics). Differentially expressed (DEPs) groups analyzed ANOVA, where a fold change ≥ 1.5 adjusted P value < 0.05 considered as significant DEPs. Partial least square discriminant analysis (PLS-DA) was used identify contributing most PR3-AAV/MPO-AAV separation STRING database analyse protein–protein interaction networks. Gene ontology, KEGG Reactome databases pathway enrichment analyses ClueGO. Results In comparison controls, 63 DEPs identified PR3-AAV 62 MPO-AAV; these, 49 common both groups. Pathway IL-17-, IL-10-, TNF-α- NF-kappa B signaling neutrophil chemotaxis among significantly enriched processes. 14 unique formed functional physical protein-protein network analysis, regulation cell proliferation, activation matrix metalloproteinases, collagen degradation IL-17- TNF-α pathways. 13 did not show any enrichment. Of top 15 group PLS-DA 11 4 MPO-AAV, respectively (Table 1). Conclusion Combining quantitative proteomics bioinformatics analyses, we have large characterizing determined their biological mechanisms. an interconnected protein processes high relevance AAV-pathogenesis. conclusion, findings may new insights similarities MPO- PR3-AAV. Table 1. results showing patients, respectively, Common vs controls Unique CCL23 EPHB4 EN-RAGE CD40 LTBR MCP-3 IL2-RA PLC PRTN3 OPN RETN ST2 TGF-alpha TIMP-1 TNF-R1 TNF-R2 TNFRSF14 U-PAR VEGFA REFERENCES: NIL. Acknowledgements: Disclosure Interests None Declared.