Serum Soluble Toll-Like Receptor 4 is a Predictive Biomarker for Acute Exacerbation and Prognosis of Idiopathic Pulmonary Fibrosis: A Retrospective Study

Overview

Journal Lung

Specialty Pulmonary Medicine

Date 2025 Mar 13

PMID 40074958

Authors

Erika Kitadai

Kakuhiro Yamaguchi

Hiroshi Iwamoto

Kiyofumi Shimoji

Shinjiro Sakamoto

Yasushi Horimasu

Takeshi Masuda

Taku Nakashima

Shinichiro Ohshimo

Hironobu Hamada

Noboru Hattori

Affiliations

Soon will be listed here.

Abstract

Purpose: Toll-like receptor 4 (TLR4) is a transmembrane receptor promoting pro-inflammatory signalling, that is associated with the pathogenesis of pulmonary fibrosis. TLR4 is abundantly expressed on monocytes and the acceleration of TLR4 signalling induces the secretion of soluble TLR4 isoforms (sTLR4) in circulation. The aim of study was to evaluate the association of serum levels of sTLR4 with acute exacerbation (AE) and prognosis of patients with idiopathic pulmonary fibrosis (IPF).

Methods: This retrospective cohort study included 97 patients with IPF and 76 healthy participants. The association of serum sTLR4 levels with the onset of AE and the prognosis in 97 patients with IPF was analyzed.

Results: No significant difference in sTLR4 serum level was observed between the patients with IPF and healthy participants. Kaplan-Meier curves showed that patients with sTLR4 ≥ 2.2 ng/mL had a significantly higher incidence of AE-IPF and a significantly lower 5-year survival rate. Univariate and multivariate Cox hazard analyses demonstrated that sTLR4 ≥ 2.2 ng/mL was significantly associated with higher incidence of AE and poorer survival. In an exploratory analysis, a weak correlation was observed between sTLR4 levels and monocyte counts, and the incidence of AE-IPF was the highest in the patients with sTLR4 ≥ 2.2 ng/mL and monocyte counts ≥ 381/μL.

Conclusion: High sTLR4 level is associated with an increased incidence of AE-IPF and poor prognosis in patients with IPF. The combination of sTLR4 level and monocyte count might be used to stratify patients with IPF according to the risk for AE via reflecting monocyte activation.

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