■观察性研究强调了自身免疫性疾病(AD)在颞下颌关节紊乱病(TMD)中的作用。然而,因果关系是否存在尚不清楚,关于TMD中哪种特定疾病具有破坏性仍存在争议。这项孟德尔随机化(MR)研究旨在评估常见AD对TMD的因果影响。
■来自已发表的14种常见AD的全基因组关联研究的遗传数据,特别是多发性硬化症(MS,N=15,283),强直性脊柱炎(AS,N=22,647),哮喘(N=408,422),乳糜泻(N=15,283),严重疾病(N=458,620),桥本甲状腺炎(N=395,640),原发性胆汁性肝硬化(PBC,N=11,375),原发性硬化性胆管炎(PSC,N=14,890),寻常型银屑病(N=483,174),类风湿性关节炎(RA,N=417,256),系统性红斑狼疮(SLE,N=23,210),1型糖尿病(T1D,N=520,580),炎症性肠病(IBD,N=34,652),和干燥综合征(SS,收集N=407,746)。此外,TMD的最新汇总数据(N=228,812)来自FinnGen数据库.通过逆方差加权(IVW)评估每个免疫性状的总体效应,加权中位数,和MR-Egger方法,并进行了广泛的敏感性分析。最后,分析了731种免疫细胞表型(N=3,757)在显着因果关系中的介导作用。
■单变量MR分析显示,遗传预测的RA(IVWOR:1.12,95%CI:1.05-1.19,p<0.001)和MS(IVWOR:1.06,95%CI:1.03-1.10,p=0.001)与TMD的风险增加相关。731种免疫细胞表型中的两种被鉴定为RA与TMD的关联中的因果介质。包括“CD25+CD8+T细胞%CD8+T细胞”(介导比例:6.2%)和“活化CD4调节性T细胞上的CD3”(5.4%)。此外,“粒细胞上的CD127”介导了MS对TMD总作用的10.6%。没有相反的方向,异质性,在分析中检测到多效性(p>0.05)。
■这项MR研究提供了关于RA或MS的遗传易感性对TMD风险增加的因果影响的新证据,可能由免疫细胞的调节介导。这些发现强调了临床医生在咨询颞下颌关节不适时更多关注RA或MS患者的重要性。提出了特异性免疫细胞的介导作用,但需要进一步研究。
UNASSIGNED: The role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs.
UNASSIGNED: Genetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves\' disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren\'s syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality.
UNASSIGNED: Univariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including \"CD25++ CD8+ T cell % CD8+ T cell\" (mediation proportion: 6.2%) and \"CD3 on activated CD4 regulatory T cell\" (5.4%). Additionally, \"CD127 on granulocyte\" mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05).
UNASSIGNED: This MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.