POS0406 miRNAs DEREGULATED IN RESPONSE TO IL17A INHIBITORS IN PSORIATIC ARTHRITIS REGULATE GENE PRODUCTS IN Rho-GTPase PATHWAYS

Background: Using transcriptomic data at initiation of therapy, we recently identified differentially expressed genes (DEGs) that separated IL-17Ai response from non-response 1 . Integration cell-type-specific DEGs with protein-protein interactions (PPIs) and further comprehensive pathway enrichment analysis revealed Rho GTPase signaling exhibited a strong signal specific to particularly the genes, RAC1 ROCK s. Objectives: To characterize microRNA (miR) profiles among responders non-responders, as it relates RHO pathway. Methods: We interrogated 20 psoriatic arthritis (PsA) patients initiating IL-17Ai. Patients achieving least low disease activity according Disease Activity Index for PsA (DAPSA) three months were classified responders. There seven (35%) thirteen non-responders (65%) in group, biologic treatment naïve (bio-naïve) previously-exposed (bio-exposed) exhibiting 50% (4/8) 25% (3/12) rate, respectively. For miR analysis, CD4 positive T cells isolated peripheral blood mononuclear using Dynabeads TM beads (ThermoFisher). Total RNA was extracted + Lexogen’s Split Extraction Kit (D-Mark Biosciences). Libraries prepared 200ng total NEXTFLEX Small RNA-Seq v3 UDIs (Bioo Scientific) sequenced on Illumina NovaSeq 6000. Raw sequencing fastq assessed quality FastQC. The miRDeep2 used trim adapter, align quantify human mature miRs miRbase (Release 22). abundance converted read counts per million, normalized limma R package identify pre- post-differentially miRs. Results: obtained 2,889 After removing reads >90% samples, 1902 high remained analysis. mirDIP v4.1 gene targets differential miRs, focused related left figure are those deregulated pre-treatment, right show post-treatment hsa-miR-3691-5p hsa-miR-3161 represent both conditions. red highlighted nodes most connected genes; thus, representing RHO-pathway centric regulators (hsa-miR-495-3p, 16-5p, 129-5p, 520h, 520g-3p), strongly regulated products (ROCK1, RHOQ, PFN2, TAOK1, DYNC1L12, MAPRE1, PAFAH1B1, ARHGAP5, MAPK1, CALM1, DIAPH2, PKN2, ITSN1). Conclusion: Pre- regulate multiple References: [1]Rahmati S, O’Rielly DD, Li Q, Codner D, Dohey A, Jenkins K, Jurisica I, Gladman Chandran V, Rahman P. Rho-GTPase pathways may differentiate TNF-alpha IL-17A inhibitors arthritis. Sci Rep. 2020 Dec 10;10(1):21703. Figure 1. Disclosure Interests: Proton Speakers bureau: AbbVie, Amgen, BMS, Celgene, Eli Lily, Janssen, Merck, Novartis, Pfizer, UCB, Consultant of: Grant/research support from: Quan Li: None declared, Dianne Codner: Darren O’Rielly: Amanda Dohey: Kari Jenkins: Dafna D Galapagos, Gilead, Vinod Paid instructor for: Employee Spousal Employment Lilly, Igor Jurisica: declared