RILITE Research Institute and AMPEL BioSolutions LLC, 250 West Main Street Suite #300, Charlottesville, VA, 22902, USA.
EMD Serono Research and Development Institute, 45 A Middlesex Turnpike, Billerica, MA, 01821, USA.
Sci Rep. 2020 Oct 15;10(1):17361. doi: 10.1038/s41598-020-74391-4.
Arthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus arthritis (LA), using osteoarthritis (OA) and rheumatoid arthritis (RA) as comparators. Knee synovia from SLE, OA, and RA patients were analyzed for differentially expressed genes (DEGs) and also by Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules of highly co-expressed genes. Genes upregulated and/or co-expressed in LA revealed numerous immune/inflammatory cells dominated by a myeloid phenotype, in which pathogenic macrophages, myeloid-lineage cells, and their secreted products perpetuate inflammation, whereas OA was characterized by fibroblasts and RA of lymphocytes. Genes governing trafficking of immune cells into the synovium by chemokines were identified, but not in situ generation of germinal centers (GCs). Gene Set Variation Analysis (GSVA) confirmed activation of specific immune cell types in LA. Numerous therapies were predicted to target LA, including TNF, NFκB, MAPK, and CDK inhibitors. Detailed gene expression analysis identified a unique pattern of cellular components and physiologic pathways operative in LA, as well as drugs potentially able to target this common manifestation of SLE.
关节炎是红斑狼疮（SLE）的常见表现，但对其潜在发病机制的认识仍不完整。因此，我们通过比较骨关节炎（OA）和类风湿关节炎（RA），分析了 SLE 滑膜的基因表达谱，以深入了解狼疮性关节炎（LA）的本质。我们分析了来自 SLE、OA 和 RA 患者的膝关节滑膜中的差异表达基因（DEGs），并通过加权基因共表达网络分析（WGCNA）来识别高度共表达基因的模块。在 LA 中上调和/或共表达的基因揭示了大量由髓样表型主导的免疫/炎症细胞，其中致病性巨噬细胞、髓系细胞及其分泌产物使炎症持续存在，而 OA 则以成纤维细胞为特征，RA 则以淋巴细胞为特征。鉴定了通过趋化因子将免疫细胞运送到滑膜中的基因，但未鉴定原位生发中心（GC）的生成。基因集变异分析（GSVA）证实了 LA 中特定免疫细胞类型的激活。预测了许多治疗方法可用于治疗 LA，包括 TNF、NFκB、MAPK 和 CDK 抑制剂。详细的基因表达分析确定了在 LA 中起作用的细胞成分和生理途径的独特模式，以及可能靶向这种 SLE 常见表现的药物。
