Dataset Information

Genetic, Immunologic, and Environmental Basis of Sarcoidosis.

ABSTRACT: Sarcoidosis is a multisystem disease with tremendous heterogeneity in disease manifestations, severity, and clinical course that varies among different ethnic and racial groups. To better understand this disease and to improve the outcomes of patients, a National Heart, Lung, and Blood Institute workshop was convened to assess the current state of knowledge, gaps, and research needs across the clinical, genetic, environmental, and immunologic arenas. We also explored to what extent the interplay of the genetic, environmental, and immunologic factors could explain the different phenotypes and outcomes of patients with sarcoidosis, including the chronic phenotypes that have the greatest healthcare burden. The potential use of current genetic, epigenetic, and immunologic tools along with study approaches that integrate environmental exposures and precise clinical phenotyping were also explored. Finally, we made expert panel-based consensus recommendations for research approaches and priorities to improve our understanding of the effect of these factors on the health outcomes in sarcoidosis.

SUBMITTER: Moller DR

PROVIDER: S-EPMC5822412 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic, Immunologic, and Environmental Basis of Sarcoidosis.

Moller David R DR Rybicki Ben A BA Hamzeh Nabeel Y NY Montgomery Courtney G CG Chen Edward S ES Drake Wonder W Fontenot Andrew P AP

Annals of the American Thoracic Society 20171201 Supplement_6

Sarcoidosis is a multisystem disease with tremendous heterogeneity in disease manifestations, severity, and clinical course that varies among different ethnic and racial groups. To better understand this disease and to improve the outcomes of patients, a National Heart, Lung, and Blood Institute workshop was convened to assess the current state of knowledge, gaps, and research needs across the clinical, genetic, environmental, and immunologic arenas. We also explored to what extent the interplay ...[more]

PMID: 29073364

Similar Datasets

Project description:COVID-19 has shown a substantial variation in the rate and severity by which it impacts different demographic groups. Specifically, it has shown a predilection towards obese patients as well as as well as other vulnerable groups including predilection of males over females, old age over young age and black races over Caucasian ones.. Single cell sequencing studies have highlighted the role of cell polarity and the co-expression of proteases, such as Furin, along with ACE2 in the genesis of coronavirus disease rather than exclusively link tissue involvement with ACE2 levels thought previously. It has also forged a connection between the genetic and immune cellular mechanisms underlying COVID infection and the inflammatory state of obese patients, offering a more accurate explanation as to why obese patients are at increased risk of poor COVID outcomes. These commonalities encompass macrophage phenotype switching, genetic expression switching, and overexpression of the pro-inflammatory cytokines, depletion of the regulatory cytokines, in situ T cell proliferation, and T cell exhaustion. These findings demonstrate the necessity of single cell sequencing as a rapid means to identify and treat those who are most likely to need hospital admission and intensive care, in the hopes of precision medicine. Furthermore, this study underlines the use of immune modulators such as Leptin sensitizers, rather than immune suppressors as anti-inflammation therapies to switch the inflammatory response from a drastic immunological type 1 response to a beneficial type 2 effective one. Highlights • ScRNA-seq focuses on the analysis of individual cells, instead of bulk cell populations, and can lead to a more insightful characterization of local microenvironments.• ScRNA-seq unleashed that tissue tropism in COVID-19 is not solely determinant by ACE2 distribution but rather by Furin.• ScRNA-seq in COVID-19 revealed two distinct types of immunologic reactions, deleterious type 1 characterized by inefficient antigen presentation, decreased memory B cells, imbalance between M1 and M2 macrophages and T cell exhaustion, and beneficial type 2 reaction which exactly the reverse of the type 1.• The immunotype 1 reaction is intriguingly similar to the immune landscape seen in obese individuals when leptin resistance sets in.• This might indicate that the use of leptin sensitizers to induce an immunologic switch from immunotype 1 to immunotype 2 can greatly improve the outcome of COVID-19 cases.• ScRNA-seq was also able to unveil the disparity between aggressive and milder strains of SARS-CoV-2, which are mainly related to their affinity to cellular activation by Furin.• The applications of ScRNA-seq may help to anticipate cases at higher risk of severe COVID-19 at their earliest encounter.

Dataset Information

Genetic, Immunologic, and Environmental Basis of Sarcoidosis.

Publications

Genetic, Immunologic, and Environmental Basis of Sarcoidosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets