RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung
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ABSTRACT:
PROVIDER: PRJNA634074 | ENA |
REPOSITORIES: ENA
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Project description:Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of CHP subjects have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF). However, the molecular relationship between CHP and IPF is not well understood. We report an RNA-seq based transcriptomic analysis for whole lung tissues from CHP, IPF and control subjects.
2020-07-01 | GSE150910 | GEO
Project description:Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5’ RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFb and TNFa/NFkB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells – reflecting this disease’s unique inflammatory T-cell driven nature – as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.
2024-07-09 | GSE271789 | GEO
Project description:RationaleMany of the interstitial lung diseases represent a diagnostic and therapeutic challenge because their clinical and even histologic features are often nonspecific. Likewise, the transcriptional signatures of most of them are unknown.ObjectiveTo compare the gene expression patterns from patients with idiopathic pulmonary fibrosis (IPF) hypersensitivity pneumonitis (HP), and nonspecific interstitial pneumonia (NSIP) using custom oligonucleotide microarrays.MethodsWe profiled lung biopsies from 15 patients with IPF, 12 with HP, and eight with NSIP. Labeled complementary ribonucleic acid was hybridized to a custom Affymetrix oligonucleotide DNA microarray using standard Affymetrix protocols. The custom array, Hu03, contained 59,619 probe sets representing an estimated 46,000 gene clusters.ResultsWe identified statistically significant gene expression signatures that characterize HP and IPF. The HP gene expression signature was enriched for genes that are functionally associated with inflammation, T-cell activation, and immune responses, whereas the IPF signature was characterized by the expression of tissue remodeling, epithelial, and myofibroblast genes. We then compared these gene expression signatures to classify NSIP, a histologic pattern that is often difficult to differentiate consistently from HP and IPF. Two cases exhibited an IPF-like gene expression, another one could be more properly classified as HP, whereas others did not resemble HP or IPF, suggesting that they may represent idiopathic NSIP.ConclusionsOur results underscore the value of gene expression signatures to classify the interstitial lung diseases and to understand pathogenic mechanisms, and suggest new ways to improve the diagnosis and treatment of patients with these diseases.
| S-EPMC2662988 | biostudies-literature
Project description:A subset of patients with hypersensitivity pneumonitis (HP) develop lung fibrosis that is clinically similar to idiopathic pulmonary fibrosis (IPF). To address the aetiological determinants of fibrotic HP, we investigated whether the common IPF genetic risk variants were also relevant in study subjects with fibrotic HP. Our findings indicate that common genetic variants in TERC, DSP, MUC5B and IVD were significantly associated with fibrotic HP. These findings provide support for a shared etiology and pathogenesis between fibrotic HP and IPF.
| S-EPMC9013199 | biostudies-literature
Project description:IL-2 inducible tyrosine kinase (Itk) is a Tec family non-receptor tyrosine kinase that is known to regulate T-helper cell differentiation and function. It has been established that Itk postively regulates T helper 17 cells. However, in a model of hypersensitivity pneumonitis we found T helper 17 cells develop independently of Itk. Therefore, we compared the transcriptomes of WT and Itk-/- T helper 17 cells following exposure with Saccharopolyspora rectivirgula by RNA sequencing.
2024-01-28 | GSE165711 | GEO
Project description:Lung microenvironments and disease progression in fibrotic hypersensitivity pneumonitis
| PRJNA763978 | ENA
Project description:N6-methyladenosine (m6A) modification plays a pivotal role in post-transcriptionally regulating gene expression and biological functions. Nonetheless, the roles of m6A modification in the regulation of chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remain unclear. Twenty-two significant m6A regulators were selected from differential gene analysis between the control and treatment groups from the GSE150910 dataset. Five candidate m6A regulators (insulin-like growth factor binding protein 2, insulin-like growth factor binding protein 3, YTH domain-containing protein 1, zinc finger CCCH domain-containing protein 13, and methyltransferase-like 3) were screened by the application of a random forest model and nomogram model to predict risks of pulmonary fibrosis. The consensus clustering method was applied to divide the treatment samples into two groups with different m6A patterns (clusters A and B) based on the 22 m6A regulators. Our study performed principal component analysis to obtain the m6A-related score of the 288 samples to quantify the two m6A patterns. The study reveals that cluster A was linked to T helper cell (Th) 2-type cytokines, while the immune infiltration of Th1 cytokines was higher in cluster B. Our results suggest that m6A cluster A is likely related to pulmonary fibrosis, indicating m6A regulators play notable roles in the occurrence of pulmonary fibrosis. The m6A patterns could be considered as biomarkers to identify CHP and IPF, which will be helpful to develop immunotherapy strategies for pulmonary fibrosis in the future.
| S-EPMC9329921 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF)
| PRJNA802122 | ENA
Project description:Rationale: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises after repeated exposure and sensitization to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease, but, to date, no study has investigated the composition of microbial communities in the lower airways in CHP.Objectives: To characterize and compare the airway microbiome in subjects with CHP, subjects with idiopathic pulmonary fibrosis (IPF), and control subjects.Methods: We prospectively recruited individuals with a CHP diagnosis (n = 110), individuals with an IPF diagnosis (n = 45), and control subjects (n = 28). Subjects underwent BAL and bacterial DNA was isolated, quantified by quantitative PCR and the 16S ribosomal RNA gene was sequenced to characterize the bacterial communities in the lower airways.Measurements and Main Results: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both subjects with IPF and subjects with CHP included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. However, in IPF, Firmicutes dominated, whereas the percentage of reads assigned to Proteobacteria in the same group was significantly lower than the percentage found in subjects with CHP. At the genus level, the Staphylococcus burden was increased in CHP, and Actinomyces and Veillonella burdens were increased in IPF. The lower airway bacterial burden in subjects with CHP was higher than that in control subjects but lower than that of those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP.Conclusions: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF, and, notably, the bacterial burden in individuals with CHP fails to predict survival.
| S-EPMC7874329 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by an abnormal activation of lung epithelium and fibroblasts, as well as an excessive accumulation of extracellular matrix. Pirfenidone was introduced as a therapeutic option for IPF and chronic hypersensitive pneumonitis (cHP), a related disease. However, high plasma concentrations, which can be achieved even at recommended doses, are frequently associated with adverse events. Hence, an extended release formulation (XP), yielding lower peak plasma concentrations, has been developed. The aim of this study was to compare the pharmacokinetic properties of XP with those of the immediate (IR) formulation in patients with IPF or cHP. Data were analyzed using two pharmacokinetic approaches, conventional non compartmental analysis and a population analysis using the nonlinear mixed effects model technique. Results observed with both approaches were consistent. Drug exposure was similar with both formulations. However, XP exhibited less concentration fluctuations and a longer mean resident time. These results suggest that XP could be a feasible option to reduce adverse events associated to pirfenidone elevated concentrations. Nevertheless, efficacy studies are required to fully document the therapeutic potential of XP.
| S-EPMC7610245 | biostudies-literature