scholarly journals The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tetsuya Hanaka ◽  
Takashi Kido ◽  
Shingo Noguchi ◽  
Sohsuke Yamada ◽  
Hirotsugu Noguchi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Healthy Volunteers ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Lung Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Inflammatory Changes

Abstract Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. Methods Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. Results Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. Conclusions PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.

scholarly journals S100A9/CD163 expression profiles in classical monocytes as biomarkers to discriminate idiopathic pulmonary fibrosis from idiopathic nonspecific interstitial pneumonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masahiro Yamashita ◽  
Yuh Utsumi ◽  
Hiromi Nagashima ◽  
Hiroo Nitanai ◽  
Kohei Yamauchi
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Healthy Volunteers ◽  
Interstitial Pneumonia ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Serum Levels ◽  
Surfactant Protein D ◽  
Nonspecific Interstitial Pneumonia ◽  
Classical Monocytes

AbstractCirculating monocytes have pathogenic relevance in idiopathic pulmonary fibrosis (IPF). Here, we determined whether the cell surface levels of two markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, expressed on CD14strongCD16− classical monocytes by flow cytometry could discriminate IPF from idiopathic nonspecific interstitial pneumonia (iNSIP). Twenty-five patients with IPF, 25 with iNSIP, and 20 healthy volunteers were prospectively enrolled in this study. The S100A9+CD163− cell percentages in classical monocytes showed a pronounced decrease on monocytes in iNSIP compared to that in IPF. In contrast, the percentages of S100A9−CD163+ cells were significantly higher in iNSIP patients than in IPF patients and healthy volunteers. In IPF patients, there was a trend toward a correlation between the percentage of S100A9+CD163− monocytes and the surfactant protein-D (SP-D) serum levels (r = 0.4158, [95% confidence interval (CI) − 0.02042–0.7191], p = 0.051). The individual percentages of S100A9+CD163− and S100A9−CD163+ cells were also independently associated with IPF through multivariate regression analysis. The unadjusted area under the receiver operating characteristic curve (ROC-AUC) to discriminate IPF from iNSIP was (ROC-AUC 0.802, 95% CI [0.687–0.928]), suggesting that these are better biomarkers than serum SP-D (p < 0.05). This preliminary study reports the first comparative characterization of monocyte phenotypes between IPF and iNSIP.

scholarly journals Genetic Variation in CCL18 Gene Influences CCL18 Expression and Correlates with Survival in Idiopathic Pulmonary Fibrosis—Part B

2020 ◽  
Vol 9 (6) ◽  
pp. 1993
Author(s):  
Canay Caliskan ◽  
Benjamin Seeliger ◽  
Benedikt Jäger ◽  
Jan Fuge ◽  
Tobias Welte ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Free Survival ◽  
Antifibrotic Therapy ◽  
Level Measurement ◽  
Chemokine Ligand

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality. CC-chemokine ligand 18 (CCL18) is predictive of survival in IPF. We described correlation of CCL18 serum levels with the genotype of rs2015086 C > T polymorphism the CCL18-gene, which was associated with survival in a pre-antifibrotic cohort (Part-A). Herein (Part-B), we aimed to validate these findings and to study the effects of antifibrotics. Two cohorts were prospectively recruited, cohort-A (n = 61, pre-antifibrotic) and cohort B (n = 101, received antifibrotics). Baseline CCL18 serum level measurement by enzyme-linked immunosorbent assay (ELISA, serially in cohort B) and genotyping of rs2015086 was performed and correlated with clinical outcomes. The CT genotype was present in 15% and 31% of patients. These patients had higher CCL18 levels compared to the TT-genotype (cohort-A: 234 vs. 115.8 ng/mL, p < 0.001; cohort B: 159.5 vs. 120 ng/mL, p = 0.0001). During antifibrotic therapy, CCL18 increased (p = 0.0036) regardless of rs2015086-genotype and antifibrotic-agent. In cohort-A, baseline CCL18-cutoff (>120 ng/mL) and CT-genotype were associated with mortality (p = 0.041 and p = 0.0051). In cohort-B, the CCL18-cutoff (>140 ng/mL) was associated with mortality (p = 0.003) and progression (p = 0.004), but not the CT/CC-genotype. In conclusion, we validated the correlation between rs2015086-genotype and CCL18 serum levels, which was predictive of (progression-free)-survival in two prospective validation cohorts.

scholarly journals Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease

2021 ◽  
Vol 10 (14) ◽  
pp. 3167
Author(s):  
Eva Cabrera Cesar ◽  
Lidia Lopez-Lopez ◽  
Estrella Lara ◽  
M. Victoria Hidalgo-San Juan ◽  
Concepcion Parrado Romero ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls

Introduction: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. Results: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86–1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60–0.97). Conclusion: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.

scholarly journals Associations of Serological Biomarkers of sICAM-1, IL-1β, MIF, and su-PAR with 3-Month Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xuran Li ◽  
Ying Zhou ◽  
Ruyi Zou ◽  
Haoran Chen ◽  
Xiaoqin Liu ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Acute Exacerbation ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Intercellular Adhesion Molecule ◽  
Rank Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Urokinase Plasminogen Activator Receptor ◽  
Serological Biomarkers

Objective. To investigate prognostic values of serum biomarkers of soluble intercellular adhesion molecule 1 (sICAM-1), macrophage migration inhibitor factor (MIF), interleukin 1β (IL-1β), and soluble urokinase plasminogen activator receptor (su-PAR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Methods. From August 2017 to November 2019, 122 consecutive IPF patients treated in our center were classified as stable IPF and AE-IPF based on the newly published international guidelines. Serum levels of four biomarkers at admission were measured by the enzyme-linked immunosorbent assay (ELISA). The primary endpoint was 3-month mortality. The log-rank test and logistic regression analysis were used to evaluate the effects of these biomarkers for survival in patients with AE-IPF. Cox proportional hazards analysis was performed to evaluate the prognostic values of serological biomarkers and clinical data. Results. Eighty-one patients were diagnosed with stable IPF, and 41 AE-IPF patients were enrolled in the study. Serum levels of sICAM-1 (p<0.001), IL-1β (p<0.001), MIF (p<0.001), and su-PAR (p<0.001) in patients with IPF were significantly increased compared to those in healthy controls. All the four biomarkers were elevated in patients with AE-IPF compared to those with stable IPF. The 3-month mortality in AE-IPF was 56.1% (23/41). Increased levels of MIF (p=0.01) and IL-1β (>5 pg/mL, p=0.033) were independent risk factors for 3-month mortality in patients with AE-IPF. Conclusions. We showed the higher serum levels of IL-1β, and MIF had prognostic values for 3-month mortality in AE-IPF. This study provided a clue to promote our understanding in the pathogenesis of the disease.

scholarly journals Serum CYR61 As A Potential Biomarker for The Diagnosis of Esophagogastric Junction Tumor

2021 ◽  
Author(s):  
Ling-Yu Chu ◽  
Jian-Yuan Zhou ◽  
Yi-Xuan Zhao ◽  
Yan-Ting Ou ◽  
Tian Yang ◽  
...  
Keyword(s):  
Early Stage ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Operating Characteristics ◽  
Tumor Patients ◽  
Chi Square ◽  
Potential Biomarker ◽  
The Difference ◽  
Normal Controls

Background：Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P&lt;0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P&gt;0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis

2021 ◽  
pp. 2004053
Author(s):  
Amisha V. Barochia ◽  
Maryann Kaler ◽  
Nargues Weir ◽  
Elizabeth M. Gordon ◽  
Debbie M. Figueroa ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Transplantation ◽  
Serum Lipids ◽  
Serum Levels ◽  
High Density Lipoproteins ◽  
Discovery Cohort ◽  
Clinical Endpoints ◽  
Multivariable Analyses ◽  
Lipids And Lipoproteins

BackgroundSerum lipoproteins, such as high density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical endpoints in IPF.MethodsClinical data and serum lipids were analyzed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicenter cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry. Associations between lipids and clinical endpoints (FVC, forced vital capacity; 6MWD, 6 min walk distance; GAP (Gender Age Physiology) index; death or lung transplantation) were examined using Pearson's correlation and multivariable analyses.ResultsSerum concentrations of small HDL particles (S-HDLPNMR), measured by nuclear magnetic resonance (NMR) spectroscopy, correlated negatively with the GAP index in the discovery cohort of IPF subjects. The negative correlation of S-HDLPNMR with GAP index was confirmed in the validation cohort of IPF subjects. Higher levels of S-HDLPNMR were associated with lower odds of death or its competing outcome, lung transplantation (OR of 0.9 for each 1 μmol·L−1 increase in S-HDLPNMR, p<0.05), at 1, 2, and 3 years from study entry in a combined cohort of all IPF subjects.ConclusionsHigher serum levels of S-HDLPNMR are negatively correlated with the GAP index, as well as with lower observed mortality or lung transplantation in IPF subjects. These findings support the hypothesis that S-HDLPNMR may modify mortality risk in patients with IPF.

scholarly journals Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 21 (22) ◽  
pp. 8812
Author(s):  
Stefania Di Mauro ◽  
Alessandra Scamporrino ◽  
Mary Fruciano ◽  
Agnese Filippello ◽  
Evelina Fagone ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Area Under The Curve ◽  
P Value ◽  
Patient Identification ◽  
Clinical Issue ◽  
Rna Molecules ◽  
Non Invasive ◽  
Non Coding Rnas ◽  
Whole Transcriptome Analysis

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2–5 years after diagnosis. Therefore, IPF patient identification represents an important and challenging clinical issue. Current research is still searching for novel reliable non-invasive biomarkers. Therefore, we explored the potential use of long non-coding RNAs (lncRNAs) and mRNAs as biomarkers for IPF. Methods: We first performed a whole transcriptome analysis using microarray (n = 14: 7 Control, 7 IPF), followed by the validation of selected transcripts through qPCRs in an independent cohort of 95 subjects (n = 95: 45 Control, 50 IPF). Diagnostic performance and transcript correlation with functional/clinical data were also analyzed. Results: 1059 differentially expressed transcripts were identified. We confirmed the downregulation of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) lncRNA, hsa_circ_0001924 circularRNA, utrophin (UTRN) and Y-box binding protein 3 (YBX3) mRNAs. The two analyzed non-coding RNAs correlated with Forced Vital Capacity (FVC)% and Diffusing Capacity of the Lung for carbon monoxide (DLCO)% functional data, while coding RNAs correlated with smock exposure. All analyzed transcripts showed excellent performance in IPF identification with Area Under the Curve values above 0.87; the most outstanding one was YBX3: AUROC 0.944, CI 95% = 0.895–0.992, sensitivity = 90%, specificity = 88.9%, p-value = 1.02 × 10−13. Conclusions: This study has identified specific transcript signatures in IPF suggesting that validated transcripts and microarray data could be useful for the potential future identification of RNA molecules as non-invasive biomarkers for IPF.

scholarly journals Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Alison E. John ◽  
Rebecca H. Graves ◽  
K. Tao Pun ◽  
Giovanni Vitulli ◽  
Ellen J. Forty ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Small Molecule ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Lung Epithelial Cells ◽  
Tgfβ Signaling ◽  
Lung Epithelial ◽  
Translational Pharmacology ◽  
Αvβ6 Integrin

Abstract The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy.

scholarly journals CA 19-9 serum levels in patients with end-stage idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs): Correlation with functional decline

2020 ◽  
Vol 17 ◽  
pp. 147997312095842
Author(s):  
Elisabetta Balestro ◽  
Gioele Castelli ◽  
Nicol Bernardinello ◽  
Elisabetta Cocconcelli ◽  
Davide Biondini ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Diseases ◽  
Lung Transplant ◽  
Functional Decline ◽  
Serum Levels ◽  
Interstitial Lung Diseases ◽  
Disease Course ◽  
Rapid Progressors ◽  
End Stage

Idiopathic pulmonary fibrosis presents a progressive and heterogeneous functional decline. CA 19-9 has been proposed as biomarker to predict disease course, but its role remains unclear. We assessed CA 19-9 levels and clinical data in end-stage ILD patients (48 IPF and 20 non-IPF ILD) evaluated for lung transplant, to correlate these levels with functional decline. Patients were categorized based on their rate of functional decline as slow (n = 20; ΔFVC%pred ≤ 10%/year) or rapid progressors (n = 28; ΔFVC%pred ≥ 10%/year). Nearly half of the entire patients (n = 32; 47%) had CA 19-9 levels ≥37kU/L. CA 19-9 levels in IPF were not different from non-IPF ILD populations, however, the latter group had a median CA 19-9 level above the normal cut-off value of 37 KU/l (60 [17–247] kU/L). Among IPF patients, CA 19-9 was higher in slow than in rapid progressors with a trend toward significance (33vs17kU/L; p = 0.055). In the whole population, CA19-9 levels were inversely related with ΔFVC/year (r = −0.261; p = 0.03), this correlation remained in IPF patients, particularly in rapid progressors (r = −0.51; p = 0.005), but not in non. Moreover, IPF rapid progressors with normal CA 19-9 levels showed the greater ΔFVC/year compared to those with abnormal CA 19-9 (0.95 vs. 0.65 L/year; p = 0.03). In patients with end-stage ILD, CA 19-9 may represent a marker of disease severity, whereas its level is inversely correlated with functional decline, particularly among IPF rapid progressors.

Sign in / Sign up

Export Citation Format

Share Document