Meng Chen, Qi Baochuang, Luo Huan, Tang Zhifang, Ren Junxiao, Shi Hongxin, Li Chuan, Xu Yongqing
Graduate School of Kunming Medical University, Kunming, Yunnan, China.
Department of Orthopaedic, 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Kunming, Yunnan, China.
Heliyon. 2024 Jul 14;10(14):e34547. doi: 10.1016/j.heliyon.2024.e34547. eCollection 2024 Jul 30.
Research shows a close association between aberrant immune reactions in osteonecrotic tissues and immune cell infiltration. However, due to limitations in sample size and dataset comprehensiveness, the causal relationship between them is not fully established. This study aims to determine whether there is a causal relationship using a larger and more diverse dataset.
We conducted a comprehensive Mendelian Randomization (MR) analysis to investigate the causal relationship between immune cell characteristics and osteonecrosis. Utilizing publicly available genetic data, we explored the causal relationships between 731 immune cell features and 604 cases from the FinnGen Finnish database, as well as 257 cases from the UK Biobank database with osteonecrosis data. The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. In addition, considering data from the two databases used in this study, a meta-analysis was conducted on the significant immune cells associated with osteonecrosis (FDR <0.05).
our findings suggested that specific immune cell signatures, such as CD20 % lymphocytes, CD62L-monocytes, and CD33br HLA DR CD14cells were associated with increased odds of osteonecrosis. In contrast, EM CD4 activated cells and DP (CD4 CD8) T cells were associated with decreased odds. Notably, osteonecrosis was associated with a potential decrease in CD45 on immature MDSC cell content.
From a genetic perspective, we demonstrated a close association between immune cells and osteonecrosis. These findings significantly enhance our understanding of the interplay between immune cell infiltration and the risk of osteonecrosis, contributing to the potential design of therapeutic strategies from an immunological standpoint.
研究表明骨坏死组织中异常免疫反应与免疫细胞浸润之间存在密切关联。然而，由于样本量和数据集全面性的限制，它们之间的因果关系尚未完全确立。本研究旨在使用更大且更多样化的数据集确定是否存在因果关系。
我们进行了全面的孟德尔随机化（MR）分析，以研究免疫细胞特征与骨坏死之间的因果关系。利用公开可用的遗传数据，我们探索了来自芬兰基因库芬兰数据库的731个免疫细胞特征与604例病例之间的因果关系，以及来自英国生物银行数据库的257例有骨坏死数据的病例之间的因果关系。主要分析采用逆方差加权（IVW）方法，并进行敏感性分析以评估主要结果的稳健性。此外，考虑到本研究中使用的两个数据库的数据，对与骨坏死相关的显著免疫细胞（FDR<0.05）进行了荟萃分析。
我们的研究结果表明，特定的免疫细胞特征，如CD20%淋巴细胞、CD62L单核细胞和CD33br HLA DR CD14细胞与骨坏死几率增加相关。相比之下，EM CD4活化细胞和DP（CD4 CD8）T细胞与几率降低相关。值得注意的是，骨坏死与未成熟MDSC细胞含量上CD45的潜在降低相关。
从遗传学角度来看，我们证明了免疫细胞与骨坏死之间存在密切关联。这些发现显著增强了我们对免疫细胞浸润与骨坏死风险之间相互作用的理解，有助于从免疫学角度设计潜在的治疗策略。
