The ABCs of Granulomatous Lung Diseases: Age-associated B Cells.
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ABSTRACT:
SUBMITTER: Polverino F
PROVIDER: S-EPMC7528779 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
The ABCs of Granulomatous Lung Diseases: Age-associated B Cells.
Polverino Francesca F Curtis Jeffrey L JL
American journal of respiratory and critical care medicine 20201001 7
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Project description:Rationale: A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients.Objectives: To measure ABC-like cell percentages in patients with lung granulomatous diseases.Methods: Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet.Measurements and Main Results: ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood.Conclusions: Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.
| S-EPMC7528799 | biostudies-literature
Project description:Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and sarcoidosis in lung cells obtained by BAL. BAL cells from CBD (n = 8), beryllium-sensitized (n = 8), sarcoidosis (n = 8), and additional progressive sarcoidosis (n = 9) and remitting (n = 15) sarcoidosis were profiled on the Illumina 450k methylation and Affymetrix/Agilent gene expression microarrays. Statistical analyses were performed to identify DNA methylation and gene expression changes associated with CBD, sarcoidosis, and disease progression in sarcoidosis. DNA methylation array findings were validated by pyrosequencing. We identified 52,860 significant (P < 0.005 and q < 0.05) CpGs associated with CBD; 2,726 CpGs near 1,944 unique genes have greater than 25% methylation change. A total of 69% of differentially methylated genes are significantly (q < 0.05) differentially expressed in CBD, with many canonical inverse relationships of methylation and expression in genes critical to T-helper cell type 1 differentiation, chemokines and their receptors, and other genes involved in immunity. Testing of these CBD-associated CpGs in sarcoidosis reveals that methylation changes only approach significance, but are methylated in the same direction, suggesting similarities between the two diseases with more heterogeneity in sarcoidosis that limits power with the current sample size. Analysis of progressive versus remitting sarcoidosis identified 15,215 CpGs (P < 0.005 and q < 0.05), but only 801 of them have greater than 5% methylation change, demonstrating that DNA methylation marks of disease progression changes are more subtle. Our study highlights the significance of epigenetic marks in lung immune response in granulomatous lung disease.
| S-EPMC6348713 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-05 | GSE110780 | GEO
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110777 | GEO
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110776 | GEO
Project description:A patient with GATA2 deficiency developed corticosteroid-responsive sterile granulomatous lung disease despite monocytopenia. The presence of B-lymphopenia, autoimmunity, an elevated level of serum B-cell-activating factor, and pulmonary plasma cell infiltration, which together suggested an underlying mechanism similar to that of combined variable immunodeficiency lung disease.
| S-EPMC11426032 | biostudies-literature
Project description:BackgroundGranulomatous Lung Diseases (GLD) encompasses a wide range of infectious and non-infectious conditions characterized by chronic inflammatory response. However, different GLD may share similar imaging findings. In this context, the purpose of this study was to outline the etiological profile and their imaging features in patients with GLD who underwent lung biopsy.MethodsPatients with granulomatous lesions in lung biopsies and previous chest CT performed from 2014 to 2017 at our institution had imaging data reviewed by three blinded radiologists. The imaging features were analyzed according to the Fleischner Society glossary. Categorical data were represented by absolute (n) and relative (%) frequency. The contingency matrices were analyzed by Pearson's Chi-square test. Interreader agreement was assessed by calculating the intraclass correlation coefficient, using kappa (κ) statistic.ResultsThirty-eight of 75 (50.7%) patients were women with a mean age of 59 ± 39 years. Infection was the most common cause of GLD (47/75, 62.7%) and Histoplasma capsulatum (27/75, 36%) was the most prevalent etiology. Nodular pattern was the most common imaging feature in histoplasmosis cases (25/27, 92.6%), whereas it occurred in half of cases (24/48) of GLD of other causes (p < 0.05). Among patients with tuberculosis, the second etiology of GLD in our study population, the most common imaging pattern was centrilobular micronodules (3/7, 42.9%), significantly more frequent than in other causes of GLD (6/68, 8.8%). Interreader agreement in detecting imaging features was almost perfect (κ = 0.88-1.00), except the nodular pattern, which had substantial agreement (κ = 0.73).ConclusionsIn our study population, the main etiologies found in patients with granulomatous disease who underwent lung biopsy were fungal or mycobacterial disease, specially histoplasmosis and tuberculosis, and nodular pattern with focal distribution was the most common imaging finding which was detected with substantial interreader agreement.
| S-EPMC7820493 | biostudies-literature
Project description:Age-associated B cells are considered a homogenoeus B cell sub-population whose accumulation has been linked to a altered immune response. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity ABCs from different health conditions.
2023-04-17 | GSE207475 | GEO
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110779 | GEO
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110778 | GEO