Department of Orthopedic, Yancheng No.1 People's Hospital, Affiliated Hospital of Medical School, Nanjing University, The First People's Hospital of Yancheng, Yancheng, 224000, China.
Department of Orthopedic, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, 215008, China.
J Transl Med. 2024 Sep 20;22(1):851. doi: 10.1186/s12967-024-05643-4.
Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis.
We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods.
GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA.
Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases.
骨关节炎（OA）和类风湿关节炎（RA）在疾病早期通常难以区分。本研究旨在通过孟德尔随机化（MR）和转录组分析探索两种疾病的异同。
我们首先对 OA 和 RA 的全基因组关联研究（GWAS）的表型数据进行相关性分析。然后，我们对 OA、RA 和正常患者的差异表达基因进行功能和通路富集分析。根据基因表达分析关节炎中免疫细胞的浸润情况。最后，用炎症细胞因子和免疫细胞作为暴露因素，关节炎作为结局进行 MR 分析。通过两种分析方法获得相同和不同的关键细胞因子和免疫细胞。
GWAS 表明 OA 和 RA 之间存在遗传相关性。OA 和 RA 的共同功能富集在对细胞因子的反应中，而差异则富集在淋巴细胞激活中。T 细胞是区分 OA 和 RA 的主要免疫细胞。MR 分析进一步表明，OA 与更多保护性细胞因子相关，而 RA 中的大多数细胞因子均具有致病性。此外，幼稚 CD4+T 细胞上的 CCR7 与 OA 呈正相关。CD4+T 细胞上的 SSC-A 与 RA 呈负相关，而 CD33-HLA DR+上的 HLA DR 与 RA 呈正相关。
本研究表明 OA 和 RA 之间免疫炎症的相似性和差异性，使我们能够更好地理解这两种疾病。
