Liu Zhengling, Kou Chengkun, Chen Xiaobo, Yang Jing, Zhu Huan, Jiao Yongning, Zhang Dongyan, Zhang Wencui, Li Liang
Department of Respiratory Medicine Department, Gansu Province Central Hospital & Gansu Provincial Maternity and Child Care Hospital, Lanzhou, Gansu, China.
The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Clin Respir J. 2025 Jul;19(7):e70111. doi: 10.1111/crj.70111.
Idiopathic pulmonary fibrosis (IPF) leads to irreversible scarring of lung tissue, resulting in deteriorating respiratory function, particularly in older adults. We aimed to explore the causative link between hypothyroidism and IPF, particularly focusing on immune cell phenotypes as mediating factors.
A two-sample Mendelian randomization (MR) approach was utilized to investigate the influence of hypothyroidism on IPF and the role of 731 distinct immune cell phenotypes as mediators. The mediating effects were quantified using the coefficient product method. Various sensitivity analyses, including Cochran's Q test for heterogeneity, MR-Egger for pleiotropy, and the "leave-one-out" method, were conducted to verify the robustness of single-nucleotide polymorphism-derived casual estimates. Statistical analyses were carried out using the R software (Version 4.3.1).
Hypothyroidism was significantly associated with increased IPF risk (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.06-1.21, p = 1.34 × 10). Of the 36 immune cell phenotypes associated with IPF, those related to the mean fluorescence intensity of B cells were the most prevalent. Mediation analysis showed that CD19 on IgD- CD27- accounted for approximately 3.68% of the effect of hypothyroidism on IPF, whereas herpesvirus entry mediator (HVEM) on T cells accounted for approximately 3.83% of this effect.
We identified a marked association between hypothyroidism and IPF. Specific immune cell phenotypes may partially mediate this relationship, although the observed effect sizes were modest. Further research is needed to validate these results in diverse populations and larger clinical trials.
特发性肺纤维化（IPF）会导致肺组织不可逆转的瘢痕形成，导致呼吸功能恶化，在老年人中尤为明显。我们旨在探讨甲状腺功能减退与IPF之间的因果关系，尤其关注免疫细胞表型作为中介因素的作用。
采用两样本孟德尔随机化（MR）方法，研究甲状腺功能减退对IPF的影响以及731种不同免疫细胞表型作为中介的作用。使用系数乘积法对中介效应进行量化。进行了各种敏感性分析，包括用于异质性的Cochran's Q检验、用于多效性的MR-Egger检验以及“留一法”，以验证单核苷酸多态性衍生的因果估计的稳健性。使用R软件（版本4.3.1）进行统计分析。
甲状腺功能减退与IPF风险增加显著相关（优势比[OR]=1.13，95%置信区间[CI]=1.06-1.21，p=1.34×10）。在与IPF相关的36种免疫细胞表型中，与B细胞平均荧光强度相关的表型最为普遍。中介分析表明，IgD-CD27-上的CD19约占甲状腺功能减退对IPF影响的3.68%，而T细胞上的疱疹病毒进入介质（HVEM）约占该影响的3.83%。
我们发现甲状腺功能减退与IPF之间存在显著关联。特定的免疫细胞表型可能部分介导了这种关系，尽管观察到的效应大小适中。需要进一步研究以在不同人群和更大规模的临床试验中验证这些结果。
