Lung microenvironments and disease progression in fibrotic hypersensitivity pneumonitis
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ABSTRACT:
PROVIDER: PRJNA763978 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR15926800.fastq.gz | Fastqsanger.gz | |||
| SRR15926801.fastq.gz | Fastqsanger.gz | |||
| SRR15926802.fastq.gz | Fastqsanger.gz | |||
| SRR15926803.fastq.gz | Fastqsanger.gz | |||
| SRR15926804.fastq.gz | Fastqsanger.gz |
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Project description:Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: We aimed to identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microCT measures, fHP cores were clustered into a mild, moderate and severe fibrosis group. Gene expression profiles were assessed using Weighted Gene Co-expression Network Analysis (WGCNA), xCell, gene ontology and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with IPF. The explant lung findings were evaluated in separate clinical fHP cohorts using tissue, bronchoalveolar lavage samples and computed tomography scans. Results: We found six molecular traits that associated with differential lung involvement. In fHP, extracellular matrix and antigen presentation/sensitization transcriptomic signatures characterized lung zones with only mild structural and histological changes, whereas signatures involved in honeycombing and B-cells dominated the transcriptome in the most severely affected lung zones. With increasing disease severity, endothelial function was progressively lost and progressive disruption in normal cellular homeostatic processes emerged. All six were also found in IPF, with largely similar associations with disease microenvironments. The molecular traits correlated with in vivo disease behaviour in a separate clinical fHP cohort. Conclusion: We identified six molecular traits which characterise the morphological progression of fHP and associate with in vivo clinical behaviour. Comparing IPF with fHP, the transcriptome landscape was determined considerably by local disease extent, rather than by diagnosis alone.
2022-01-01 | GSE184316 | 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:Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis
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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: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:The diagnosis of hypersensitivity pneumonitis (HP) relies on the clinical evaluation of a number of features, including a history of significant exposure to potentially causative antigens, physical examination, chest CT scan appearances, bronchoalveolar lavage lymphocytosis, and, in selected cases, histology. The presence of fibrosis is associated with higher morbidity and mortality. Differentiating fibrotic HP from the idiopathic interstitial pneumonias can be a challenge. Furthermore, even in the context of a clear diagnosis of fibrotic HP, the disease behaviour can parallel that of idiopathic pulmonary fibrosis in a subgroup, with inexorable progression despite treatment. We review the current knowledge on the diagnosis, management, and prognosis of HP with particular focus on the fibrotic phenotype.
| S-EPMC5483872 | biostudies-literature
Project description:RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung
| PRJNA634074 | ENA
Project description:The Tec family kinase Itk is not required for Th17 responses during Hypersensitivity pneumonitis
| PRJNA695519 | ENA
Project description:Transcriptional analysis of non-fibrotic NAFLD progression
| PRJNA634922 | ENA
Project description:BackgroundHypersensitivity pneumonitis (HP) is a syndrome caused by sensitisation to inhaled antigens that leads to an abnormal immune response in the airways and lung parenchyma. Some patients previously diagnosed with certain types of fibrotic interstitial lung diseases (f-ILDs), including fibrotic HP (f-HP), are susceptible to develop a progressive fibrosing phenotype (PF-ILD), despite initial state-of-the-art management.ObjectivesTo characterise a cohort of patients with a multidisciplinary diagnosis (MTD) of chronic f-HP, who were followed up in an ILD outpatient clinic of a hospital in Portugal, and to assess the prevalence of PF-ILD criteria in these patients.MethodsData were collected from all patients with a definite or provisional diagnosis of f-HP after a multidisciplinary team discussion. Patients were followed up between December 2014 and July 2019. Data included clinical characteristics, high-resolution chest tomography (HRCT) disease patterns, lung function tests, bronchoalveolar lavage and further immunological work-up, biopsy reports (conventional transbronchial lung biopsy, transbronchial lung cryobiopsy or surgical video-assisted thoracoscopic lung biopsy), all ILD multidisciplinary team records and diagnostic confidence levels. Patients were assessed according to PF-ILD criteria as defined in the INBUILD trial.ResultsWe identified 83 patients with an MTD of HP, who had been followed up for at least 12 months. Of these, 63 (75.9%) were diagnosed with f-HP. Of the 63 f-HP patients, 33.3% (n=21) fulfilled the predefined criteria for PF-HP: 66.7% had a relative decline of ≥10% forced vital capacity (FVC); 5% a relative decline of 5 - 9% FVC, with worsening symptoms or increased fibrosis on HRCT; and 23.8% had worsening respiratory symptoms with radiological progression.ConclusionThis single-centre cohort study demonstrated that a third of f-HP patients presented with PF-ILD, as determined by progression during initial standard-of-care treatment. A usual interstitial pneumonia (UIP)/UIP-like pattern was present in >70% of patients with f-HP, and two-thirds of these patients had an FVC decline of ≥10%. PF-HP patients were also more exacerbation prone. According to recent trial data, this segment of patients can be considered possible candidates for antifibrotic treatment, with a reasonable prospect of effectiveness. Further efforts should focus on refining knowledge of longitudinal behaviour of large multicentric cohorts of f-HP patients, establishing a consensual and uniform definition of progression for use in clinical practice, as well as developing prognostic prediction tools to better (and early) inform the disease course.
| S-EPMC9929648 | biostudies-literature