Candidate Role for Toll-like Receptor 3 L412F Polymorphism and Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

McElroy, Aoife; Invernizzi, Rachele; Laskowska, Joanna; O’Neill, Andrew; Doroudian, Mohammad; Moghoofei, Mohsen; Mostafaei, Shayan; Li, Feng; Przybylski, Alexander A.; O’Dwyer, David N.; Bowie, Andrew; Fallon, Padraic G.; Maher, Toby M.; Hogaboam, Cory M.; Molyneaux, Philip L.; Hirani, Nik; Armstrong, Michelle E.; Donnelly, Seamas C

doi:10.1164/rccm.202010-3880oc

Cited by 16 publications

(10 citation statements)

References 49 publications

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“…37 A recent study by McElroy et al suggested that viral and bacterial infections induce AE-related death in IPF. 38 In response to infection and dysbiosis of the lung microbiome, inflammatory markers, such as WBC counts, CRP levels, and PCT levels, were elevated, [39][40][41] which is consistent with our results. We also observed that the AE-IPF group had a substantially higher A-aDO 2 than the stable IPF group, which reflected marked pulmonary diffusion impairment in patients with AE-IPF.…”

supporting

confidence: 90%

The Role of Serum 1,25-Dihydroxy Vitamin D3 and PCT in Idiopathic Pulmonary Fibrosis

Li¹,

Zhai²,

Zhang³

2022

IJGM

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Biomarkers for the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) are urgently needed to provide better patient management. We aimed to investigate whether serum 1,25(OH) 2 D 3 (1,25-dihydroxy vitamin D 3 ) levels predict AE-IPF and whether they could be a potential prognostic biomarker for IPF. Participants and Methods: This prospective study included 72 patients with IPF (31 with stable IPF and 41 with AE-IPF). All participants were recruited during hospitalisation at Tianjin Chest Hospital and were followed up for at least 12 months. Demographics, comorbidities, arterial blood gas, and serum biochemical profile, radiological features, and anti-fibrotic therapy were evaluated. Serum concentrations of 1,25(OH) 2 D 3 and transforming growth factor beta1 (TGFβ1) were detected using enzyme-linked immunosorbent assay (ELISA). Risk factors for AE-IPF were identified using multivariate analysis. Prognostic factors were assessed using Kaplan-Meier and Cox regression analyses.Results: Baseline values of alveolar-arterial oxygen difference (A-aDO 2 ) (40.85 mmHg vs 29.2 mmHg, p =0.035), white blood cell counts (10.09 ± 4.2×10 9 /L vs 7.46 ± 7.84×10 9 /L, p <0.001), percentage of monocytes (7.36 ± 1.36% vs 6.6 ± 1.2%, p =0.017), C-reactive protein (CRP) (2.1 mg/dL vs 1.12 mg/dL, p =0.015) and procalcitonin (PCT) (36.59% vs 3.23%, p <0.001) were significantly higher in AE-IPF patients than in stable IPF patients. Instead, the mean concentration of serum calcium and 1,25(OH) 2 D 3 at baseline were higher in IPF patients with stable disease than in those with acute exacerbation (2.17 ± 0.13 nmol/L vs 2.09 ± 0.13 nmol/L, p =0.023 and 16.62 pg/mL vs 11.58 pg/mL, p <0.001, respectively). In multivariate analysis, a higher proportion of patients with lower serum 1,25(OH) 2 D 3 levels experienced AE-IPF (OR 0.884, 95% CI 0.791-0.987, p =0.029), and rising serum PCT level (PCT > 0.05 ng/mL) was associated with an increased risk of mortality (HR 3.664, 95% CI 1.010-12.900, p =0.043). Conclusion:Decreased serum 1,25(OH) 2 D 3 is associated with an increased risk of acute exacerbation for patients with IPF. A high serum PCT level is predictive of worse prognosis in IPF patients. 1,25(OH) 2 D 3 may be a potential biomarker for AE-IPF, while PCT could be a prognostic biomarker for IPF.

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supporting

confidence: 90%

The Role of Serum 1,25-Dihydroxy Vitamin D3 and PCT in Idiopathic Pulmonary Fibrosis

Li¹,

Zhai²,

Zhang³

2022

IJGM

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“…O'Dwyer et al [ 51 ] found that TLR3 L412F was associated with lung function decline and high mortality in a bleomycin- (BLM-) induced pulmonary fibrosis mouse model. McElroy et al [ 52 ] revealed that this effect might be because 412 F-heterozygous patients were likely to suffer from bacterial and viral infections. Using the single-cell gene sequencing dataset, Li et al [ 53 ] confirmed that lung macrophages express Toll-interacting protein (TOLLIP) which is an inhibitory adaptor protein that acts downstream of TLRs [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022

Zhao

Wang

et al. 2023

Journal of Immunology Research

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Background. Idiopathic pulmonary fibrosis (IPF) is a disease with significant morbidity, progressive deterioration of lung function till death, and lack of effective treatment options. This study aims to explore the global research trends in IPF and immune response to predict the research hotspot in the future. Materials and methods. All related publications on IPF and immune response since the establishment of diagnostic criteria for IPF were retrieved using the Web of Science (WOS) database. VOSviewer, GraphPad Prism 6, CiteSpace version 5.6. R5 64-bit, and a bibliometrics online platform were used to extract and analyze the trends in relevant fields. Results. From March 1, 2000, to September 30, 2022, a total of 658 articles with 25,126 citations met the inclusion criteria. The United States ranked first in number of publications (n = 217), number of citations (n = 14,745), and H-index (62). China ranked second in publications (n = 124) and seventh and fifth for citation frequency and H-index, respectively. The American Journal of Respiratory and Critical Care Medicine (impact factor = 30.528) published the most articles in the field. The author Kaminski N. from the United States was the most influential author with 26 publications and an H-index of 24. Among the 52 keywords that co-occurred at least 20 times, the main keywords were concentrated in “Inflammation related” and “Biomarker related” clusters. “biomarker” (AAY 2018.64, 25 times) was a newly emerged keyword. Conclusions. The United States has an unequivocal advantage in IPF and immunization, but China shows a faster developing trend. The American Journal of Respiratory and Critical Care Medicine should be prioritized for leading articles. This study indicates that exploration of ideal immune-related biomarkers to provide evidence for the clinical work of IPF might be a hotspot in the near future.

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“…Study demonstrated that PI3 [367], CX3CR1 [368], S100A12 [369], MPO (myeloperoxidase) [370], CD5L [371], S100A8 [372], CXCL11 [373], BPI (bactericidal permeability increasing protein) [374], AQP4 [375], BDNF (brain derived neurotrophic factor) [376], CXCL10 [377], CCL8 [378], S100A9 [379], IL1B [240], CXCR1 [380], CXCR2 [381], ABCA3 [382], GPR18 [383], VIP (vasoactive intestinal peptide) [384], KL (klotho) [385], TLR3 [386], NLRP12 [387], GATA3 [388], CCR2 [389], TLR7 [390], CAV1 [391], CR1 [392], DLL4 [393] and AQP5 [394] were essential for the induction of airway inflammation. CX3CR1 [395], S100A12 [396], MPO (myeloperoxidase) [397], RXFP1 [398], S100A8 [399], CXCL11 [373], CBS (cystathionine beta-synthase) [400], WNT7A [401], BDNF (brain derived neurotrophic factor) [402], CXCL10 [403], CCL8 [404], FCGR3B [405], S100A9 [406], IL1B [407], CXCR2 [408], WNT3A [409], BMI1 [410], STC1 [411], ABCA3 [412], CD36 [413], TRIB3 [414], GPX3 [415], FGF2 [416], FASN (fatty acid synthase) [417], SHH (sonic hedgehog signaling molecule) [418], DACH1 [419], FGF9 [420], SLC7A11 [421], VIP (vasoactive intestinal peptide) [422], KL (klotho) [423], BMPR2 [424], APOA1 [425], LRRK2 [426], TLR3 [427], GATA3 [428], RSPO2 [429], CCR2 [430], NEK7 [431], BMPER (BMP binding endothelial regulator) [432], CAV1 [433], CR1 [434], TFPI (tissue factor pathway inhibitor) [435], AP1S2 […”

Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analysis of DEGs were performed. Then, a protein protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst database was used to construct the targeted microRNAs (miRNAs) and transcription factors (TFs) of the hub genes. Finally receiver operating characteristic (ROC) curve analysis was used to validates the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 and EFHC2 were selected. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Candidate Role for Toll-like Receptor 3 L412F Polymorphism and Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Cited by 16 publications

References 49 publications

The Role of Serum 1,25-Dihydroxy Vitamin D3 and PCT in Idiopathic Pulmonary Fibrosis

The Role of Serum 1,25-Dihydroxy Vitamin D3 and PCT in Idiopathic Pulmonary Fibrosis

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

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