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

IF 4.6 2区医学 Q1 RESPIRATORY SYSTEM

Lung Pub Date : 2025-03-12 DOI:10.1007/s00408-025-00800-y

Erika Kitadai, Kakuhiro Yamaguchi, Hiroshi Iwamoto, Kiyofumi Shimoji, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Taku Nakashima, Shinichiro Ohshimo, Hironobu Hamada, Noboru Hattori

{"title":"Serum Soluble Toll-Like Receptor 4 is a Predictive Biomarker for Acute Exacerbation and Prognosis of Idiopathic Pulmonary Fibrosis: A Retrospective Study.","authors":"Erika Kitadai, Kakuhiro Yamaguchi, Hiroshi Iwamoto, Kiyofumi Shimoji, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Taku Nakashima, Shinichiro Ohshimo, Hironobu Hamada, Noboru Hattori","doi":"10.1007/s00408-025-00800-y","DOIUrl":null,"url":null,"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.","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"43"},"PeriodicalIF":4.6000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903555/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lung","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00408-025-00800-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

血清可溶性toll样受体4是特发性肺纤维化急性加重和预后的预测性生物标志物：一项回顾性研究

目的：toll样受体4 （TLR4）是一种促进促炎信号传导的跨膜受体，与肺纤维化的发病机制有关。TLR4在单核细胞上大量表达，TLR4信号传导的加速诱导循环中可溶性TLR4亚型（sTLR4）的分泌。本研究旨在评价血清sTLR4水平与特发性肺纤维化（IPF）患者急性加重（AE）及预后的关系。方法：回顾性队列研究纳入97例IPF患者和76名健康受试者。分析97例IPF患者血清sTLR4水平与AE发病及预后的关系。结果：IPF患者与健康人血清sTLR4水平无显著差异。Kaplan-Meier曲线显示，sTLR4≥2.2 ng/mL的患者AE-IPF发生率显著增高，5年生存率显著降低。单因素和多因素Cox风险分析显示，sTLR4≥2.2 ng/mL与AE的高发生率和较差的生存率显著相关。探索性分析发现，sTLR4水平与单核细胞计数呈弱相关，且在sTLR4≥2.2 ng/mL、单核细胞计数≥381/μL的患者中AE-IPF发病率最高。结论：高sTLR4水平与AE-IPF患者发病率升高及预后不良相关。结合sTLR4水平和单核细胞计数，可通过反映单核细胞活化情况，对IPF患者进行AE风险分级。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Lung 医学-呼吸系统

CiteScore

9.10

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.