Role of Immune Cells in Mediating the Effect of Hypothyroidism on Idiopathic Pulmonary Fibrosis

Abstract

Introduction

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.

Methods

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).

Results

Hypothyroidism was significantly associated with increased IPF risk (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.06–1.21, p = 1.34 × 10⁻⁴). 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.

Conclusion

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.