Rho-GTPase pathways may differentiate treatment response to TNF-alpha and IL-17A inhibitors in psoriatic arthritis
| Autor: | Proton Rahman, Dafna D. Gladman, Amanda Dohey, Vinod Chandran, Darren D. O’Rielly, Quan Li, Kari Jenkins, D. Codner, Igor Jurisica, Sara Rahmati |
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| Rok vydání: | 2020 |
| Předmět: |
rac1 GTP-Binding Protein
rho GTP-Binding Proteins 0301 basic medicine Necrosis Science RAC1 GTPase Antibodies Monoclonal Humanized Article Transcriptome 03 medical and health sciences Psoriatic arthritis Rheumatic diseases 0302 clinical medicine Rheumatology Spondyloarthritis medicine Gene 030203 arthritis & rheumatology Multidisciplinary Tumor Necrosis Factor-alpha business.industry Arthritis Psoriatic Interleukin-17 Adalimumab Antibodies Monoclonal medicine.disease Biological Therapy Treatment Outcome 030104 developmental biology Antirheumatic Agents Cancer research Medicine Tumor necrosis factor alpha medicine.symptom Signal transduction business Signal Transduction |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Biological therapies have dramatically improved the therapeutic landscape of psoriatic arthritis (PsA); however, 40–50% of patients are primary non-responders with response rates declining significantly with each successive biological therapy. Therefore, there is a pressing need to develop a coherent strategy for effective initial and subsequent selection of biologic agents. We interrogated 40 PsA patients initiating either tumour necrosis factor inhibitors (TNFi) or interleukin-17A inhibitors (17Ai) for active PsA. Patients achieving low disease activity according to the Disease Activity Index for PsA (DAPSA) at 3 months were classified as responders. Baseline and 3-month CD4+ transcript profiling were performed, and novel signaling pathways were identified using a multi-omics profiling and integrative computational analysis approach. Using transcriptomic data at initiation of therapy, we identified over 100 differentially expressed genes (DEGs) that differentiated IL-17Ai response from non-response and TNFi response from non-response. Integration of cell-type-specific DEGs with protein–protein interactions and further comprehensive pathway enrichment analysis revealed several pathways. Rho GTPase signaling pathway exhibited a strong signal specific to IL-17Ai response and the genes, RAC1 and ROCKs, are supported by results from prior research. Our detailed network and pathway analyses have identified the rewiring of Rho GTPase pathways as potential markers of response to IL17Ai but not TNFi. These results need further verification. |
| Databáze: | OpenAIRE |
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