Serum high‐mobility group box 1 is associated with the onset and severity of acute exacerbation of idiopathic pulmonary fibrosis

Abstract

Background and objective High‐mobility group box 1 (HMGB1) is a known mediator of acute lung injury through the acceleration of pro‐inflammatory –signalling. Previous studies showed that HMGB1 is increased in the lung and circulation of patients with acute exacerbation of idiopathic pulmonary fibrosis (AE‐IPF). This study investigated the predictive value of circulatory HMGB1 for disease progression and prognosis of IPF in the stable phase and AE phase. Methods In total, 76 patients with stable IPF, 17 patients with AE‐IPF, 37 patients with chronic obstructive pulmonary disease (COPD) and 74 healthy controls were included. Serum HMGB1 levels were compared among the four groups and the associations of HMGB1 levels with the onset of AE and prognosis were evaluated in patients with stable IPF. The prognostic value of HMGB1 was determined in AE‐IPF. Results Serum HMGB1 levels in patients with stable IPF were significantly higher than those in healthy controls, and in patients with AE‐IPF they were even higher than the levels in either of these groups (6.26 ± 5.27, 3.42 ± 2.69 and 19.20 ± 16.76 ng/mL, respectively). There was no significant difference in serum HMGB1 levels between stable IPF patients and COPD patients. Higher levels of HMGB1 were associated with earlier onset of AE in stable IPF patients and with shorter survival in AE‐IPF patients (P = 0.030 and 0.001, respectively). Conclusion Higher levels of serum HMGB1 predict earlier onset of AE in stable IPF patients and shorter survival in AE‐IPF patients, indicating that HMGB1 is associated with acute deterioration of the disease.

The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

“…It directly binds to high motility group box 1 (HMGB1) secreted by inflammatory cells and Lewis Y antigen in lipopolysaccharide on gram-negative bacteria [44], by which it prevents these molecules from interacting with their own receptors and suppresses the signal transduction to the down-stream pro-inflammatory pathway [45]. As an elevation of serum HMGB1 was noted in patients with acute lung injury [46] and a higher level of the molecule is reported to predict shorter survival of patients with AE of IPF [47], thrombomodulin, which plays a role in controlling the effect of HMGB1, may be essential in the pathogenesis of the disease. Previous studies demonstrated that thrombomodulin is excessively secreted into bloodstream in severe illnesses such as sepsis and ARDS [48,49].…”

Role of Atypical Chemokines and Chemokine Receptors Pathways in the Pathogenesis of COPD

“…Serum HMGB1 levels are increased in stable COPD patients (n=37, mean age 71 years) and in stable idiopathic pulmonary fibrosis (IPF) patients (n=76, mean age 67 years) compared to smokers with normal lung function (n=74, mean age 54 years), however there are no significantly differences in serum HMGB1 levels between COPD and IPF groups [81]. Conversely, increased serum HMGB1 levels are reported in COPD patients during exacerbation (n=40, mean age 64 years), compared with the same patients during the stable phase.…”

“…High-mobility group protein B1 Serum + [78,81,85] and = [80] Spontaneous sputum + [78] Lung tissue + [79] BAL + [86][87] and - [88] Serum + [82][83] Cathelicidin (LL-37) Serum = [152,178] and - [183] Spontaneous sputum + [152,178] Lung tissue + [185] BAL + in mild disease [179] and -in severe disease [179] Serum + [181] Spontaneous sputum + [182] Induced sputum + [181] Histatins Lactoferrin Spontaneous sputum + [219] Spontaneous sputum - [182] -defensins BAL + [274] Serum = [276] and - [279] Spontaneous sputum + [180,276] -defensins Spontaneous sputum - [273] Lung tissue + [269][270] Spontaneous sputum = [180] BAL + [277] Hepcidin Serum - [288] Lysozyme Spontaneous sputum - [182] Chemerins…”

The perplexing role of RAGE in pulmonary fibrosis: causality or casualty?

“…In contrast to trends of sRAGE, various RAGE ligands are elevated in lungs and systemically in subjects with IPF, many of which have strong pro-inflammatory effects. 44 , 125 , 126 The S100 calcium-binding proteins S100A8 and S100A9 are danger signals (or alarmins), which together can form a heterodimer referred to as calprotectin. S100A8/A9 signals through both TLR4 and RAGE and has pro-inflammatory and antimicrobial effects.…”