Kyung Eun Lee1,2, Seyoung Mun3,4, Kyudong Han5,6,7, Seunghee Cha8, Song-Mi Kim3,4, Wonseok Shin4,9, Won Jung1, Joon Paek10, Jungnam Lee11, Erin Hudson12, Wesley H Reeves12. 1. Department of Oral Medicine, School of Dentistry, Jeonbuk National University, Jeonju, 54896, Republic of Korea. 2. Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54896, Republic of Korea. 3. Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan, 31116, Republic of Korea. 4. Department of Microbiology, College of Science and Technology, Dankook University, Cheonan, 31116, Republic of Korea. 5. Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan, 31116, Republic of Korea. kyudong.han@gmail.com. 6. Department of Microbiology, College of Science and Technology, Dankook University, Cheonan, 31116, Republic of Korea. kyudong.han@gmail.com. 7. Department of Academy-Industry Cooperation, Dankook University, 409, Cheonan, Chungcheongnam-do, 330-714, Republic of Korea. kyudong.han@gmail.com. 8. Division of Oral Medicine, Department of Oral and Maxillofacial Diagnostic Sciences, Center for Orphaned Autoimmune Disorders, College of Dentistry, University of Florida, UF Health Oral Medicine, 1395 Center Drive, Gainesville, FL, 32610, USA. SCHA@dental.ufl.edu. 9. NGS Clinical Laboratory, Dankook University Hospital, Cheonan, 31116, Republic of Korea. 10. Division of Oral Medicine, Department of Oral and Maxillofacial Diagnostic Sciences, Center for Orphaned Autoimmune Disorders, College of Dentistry, University of Florida, UF Health Oral Medicine, 1395 Center Drive, Gainesville, FL, 32610, USA. 11. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, FL, 32610, USA. 12. Division of Rheumatology and Clinical Immunology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Abstract
BACKGROUND: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). OBJECTIVE: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. METHODS: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. RESULTS: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. CONCLUSIONS: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.
BACKGROUND: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). OBJECTIVE: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. METHODS: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. RESULTS: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. CONCLUSIONS: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.
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