POS0187 DRUG REPURPOSING FOR TREATING LUPUS NEPHRITIS BASED ON TRANSCRIPTOME PROFILING AND AUTOIMMUNITY-RELATED SEROLOGICAL MARKERS

Background Lupus nephritis (LN) is one of the most severe organ manifestations systemic lupus erythematosus (SLE) and constitutes an important cause morbidity death among patients with SLE [1]. The associated renal injury, ultimately damage, result immune-mediated process which involves leukocytes, immune complexes, complement cytokines [2]. Objectives Methods We analysed differentially expressed genes (DEGs), pathways their druggability via Drug Gene Interaction database (DGIdb) [3] in active LN (n=41) versus healthy controls (HC; n=497), eQTLs or past (n=87), based on validated (identified two independent populations) DEGs (n=350) vs HC (n=497), whole blood collected within frame European PRECISESADS consortium [4]. Genome-wide RNA-sequencing genotyping was previously performed by Illumina assays, serum levels 17 18 autoantibodies were using a Luminex assay, ELISA, IDS-iSYS SPAPLUS analyser Results A total 6 869 significant identified compared HC. Of these, 1010 tagged to 34 KEGG including 24 |fold change (FC)| > 1.5, cis-eQTLs 3 trans-eQTLs, 1 gene from that differed significantly between Moreover, 2446 216 Reactome included 85 |FC| 21 5 These could be targeted 203 different drugs, proteasome inhibitor bortezomib interfering cathepsin B (CTSB) regulation cyclophosphamide tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) being particular interest. Conclusion Integrated multilevel omics analysis revealed set enriched potential interest for future drug investigation. prospect inhibition implicated. References [1]Croca SC, Rodrigues T, Isenberg DA. Assessment cohort over 30-year period. Rheumatology (Oxford). 2011 Aug; 50(8):1424-1430. [2]Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. nephritis. Nat Rev Dis Primers. 2020 Jan 23; 6(1):7. [3]Wagner AH, Coffman AC, Ainscough BJ, Spies NC, Skidmore ZL, Campbell KM, et al. DGIdb 2.0: mining clinically relevant drug-gene interactions. Nucleic Acids Res. 2016 4; 44(D1):D1036-1044. [4]Barturen G, Babaei S, Català-Moll F, Martínez-Bueno M, Makowska Z, Martorell-Marugán J, Integrative Analysis Reveals Molecular Stratification Systemic Autoimmune Diseases. Arthritis Rheumatol. 2021 Jun; 73(6):1073-1085. [5]Kanehisa Furumichi Tanabe Sato Y, Morishima K. KEGG: new perspectives genomes, pathways, diseases drugs. 2017 45(D1):D353-d361. [6]Jassal B, Matthews L, Viteri Gong C, Lorente P, Fabregat A, reactome pathway knowledgebase. 8; 48(D1):D498-d503. Acknowledgements Clinical Consortium Disclosure Interests None declared