He Jianquan, Chen Xiayun
Department of Stomatology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People's Republic of China.
J Pain Res. 2024 Nov 16;17:3791-3800. doi: 10.2147/JPR.S486817. eCollection 2024.
Even with significant progress has been made in elucidating the pathogenesis of temporomandibular disorders (TMD), the pathophysiology of temporomandibular joint (TMJ) pain is still obscure. Our study aimed to explore whether there is a causal link between immune cells and TMD-related pain.
Based on the TMD-related pain data obtained from the FinnGen Research Consortium and the 731 immune traits extracted from the GWAS Catalog and utilized a two sample Mendelian Randomization (MR) method, with immune cell as the exposure and TMD-related pain as the outcome. MR analyses were conducted employing the inverse-variance weighting method (IVW) as the primary analytical method to evaluate the causal association. Sensitivity analyses were conducted to enhance the robustness, heterogeneity and horizontal pleiotropy of the results. A reverse MR analysis was also conducted for immune cell traits identified in the initial MR analysis.
After false discovery rate (FDR) correction, two immune traits were observed and found to be significantly associated with TMD-related pain: Hematopoietic Stem Cell absolute count (OR=0.954, 95% CI= 0.9330.976), and HLA DR+ CD4+ T cell (OR=1.040, 95% CI=1.0191.061). On the reverse MR analysis, no significantly associated results were found in causal effects of TMD-related pain on immune traits.
Our study showed a potential causal relationship between immune cells and TMD-related pain, eliminating reverse causality. These discoveries significantly enhance our knowledge of the interaction between immune traits and TMD-related pain, opening new possibilities for designing treatment from an immunological perspective.
尽管在阐明颞下颌关节紊乱病（TMD）的发病机制方面已取得显著进展，但颞下颌关节（TMJ）疼痛的病理生理学仍不清楚。我们的研究旨在探讨免疫细胞与TMD相关疼痛之间是否存在因果关系。
基于从芬兰基因研究联盟获得的TMD相关疼痛数据以及从全基因组关联研究（GWAS）目录中提取的731种免疫特征，并采用两样本孟德尔随机化（MR）方法，以免疫细胞为暴露因素，TMD相关疼痛为结局。采用逆方差加权法（IVW）作为主要分析方法进行MR分析，以评估因果关联。进行敏感性分析以增强结果的稳健性、异质性和水平多效性。还对初始MR分析中确定的免疫细胞特征进行了反向MR分析。
经过错误发现率（FDR）校正后，观察到两种免疫特征与TMD相关疼痛显著相关：造血干细胞绝对计数（OR = 0.954，95%置信区间= 0.9330.976），以及HLA DR + CD4 + T细胞（OR = 1.040，95%置信区间= 1.0191.061）。在反向MR分析中，未发现TMD相关疼痛对免疫特征的因果效应有显著相关结果。
我们的研究显示了免疫细胞与TMD相关疼痛之间存在潜在因果关系，排除了反向因果关系。这些发现显著增进了我们对免疫特征与TMD相关疼痛之间相互作用的认识，为从免疫学角度设计治疗方法开辟了新的可能性。
