Gao Chenghao, Pu Hongxu, Zeng Yifan, Xiao Jun
Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People's Republic of China.
BMC Musculoskelet Disord. 2025 May 22;26(1):504. doi: 10.1186/s12891-025-08735-4.
Knee osteoarthritis (OA) is a common degenerative joint disease that affects millions of people worldwide. Inflammation is one of the key pathogenic factors of knee OA. However, the causal relationship between immune cells and knee OA development remains unclear. Herein, we used Mendelian randomization (MR) analysis to evaluate causal relationship between 731 immune cells and knee OA. Several methods were applied to ensure the robustness of our results, including inverse-variance weighted (IVW), simple mode, weighted median, weighted mode, and MR-Egger. We found that 23 immune cell phenotypes were causally associated with knee OA (P < 0.05), including various subpopulations of B cells, T cells, TBNK (T cells, B cells, Natural Killer cells) and monocytes, which was confirmed by heterogeneity, sensitivity, and pleiotropy tests. B cells had dominant effects on OA development, and specifically, our findings suggest that BAFF-R in IgD + CD38- unswitched memory B cells may have a protective role, whereas CD25 in IgD + CD24 + B cells appears to be associated with increased risk, pending further validation. Moreover, a higher population of regulatory T (Treg) cells indicated a higher risk of OA and reversely, OA could induce Treg differentiation. Collectively, our study identified several immune cells that were closely related to OA development, which provided novel insights into the pathogenesis of OA and therapeutic targets for OA treatment.
膝关节骨关节炎（OA）是一种常见的退行性关节疾病，影响着全球数百万人。炎症是膝关节OA的关键致病因素之一。然而，免疫细胞与膝关节OA发展之间的因果关系仍不清楚。在此，我们使用孟德尔随机化（MR）分析来评估731种免疫细胞与膝关节OA之间的因果关系。应用了几种方法来确保我们结果的稳健性，包括逆方差加权（IVW）、简单模式、加权中位数、加权模式和MR-Egger。我们发现23种免疫细胞表型与膝关节OA存在因果关联（P < 0.05），包括B细胞、T细胞、TBNK（T细胞、B细胞、自然杀伤细胞）和单核细胞的各种亚群，这通过异质性、敏感性和多效性测试得到了证实。B细胞对OA发展具有主导作用，具体而言，我们的研究结果表明，IgD + CD38-未转换记忆B细胞中的BAFF-R可能具有保护作用，而IgD + CD24 + B细胞中的CD25似乎与风险增加有关，有待进一步验证。此外，较高比例的调节性T（Treg）细胞表明OA风险较高，反之，OA可诱导Treg分化。总的来说，我们的研究确定了几种与OA发展密切相关的免疫细胞，这为OA的发病机制和OA治疗的靶点提供了新的见解。
