Defining CD4 T helper and T regulatory cell endotypes of progressive and remitting pulmonary sarcoidosis (BRITE): protocol for a US-based, multicentre, longitudinal observational bronchoscopy study.

Autor:	Koth LL; Department of Medicine, University of California San Francisco, San Francisco, California, USA., Harmacek LD; Center for Genes, Environment, & Health, National Jewish Health, Denver, Colorado, USA., White EK; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, Colorado, USA., Arger NK; Department of Medicine, University of California San Francisco, San Francisco, California, USA., Powers L; Department of Medicine, University of Iowa, Iowa City, Iowa, USA., Werner BR; Department of Medicine, University of Iowa, Iowa City, Iowa, USA., Magallon RE; Center for Genes, Environment, & Health, National Jewish Health, Denver, Colorado, USA., Grewal P; Department of Medicine, University of California San Francisco, San Francisco, California, USA., Barkes BQ; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado, USA., Li L; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado, USA., Gillespie M; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado, USA., Collins SE; Division of Pulmonary and Critical Care Medicine, Baltimore, Maryland, USA., Cardenas J; Department of Medicine, University of California San Francisco, San Francisco, California, USA., Chen ES; Division of Pulmonary and Critical Care Medicine, Baltimore, Maryland, USA., Maier LA; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado, USA., Leach SM; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, Colorado, USA., O'Connor BP; Center for Genes, Environment, & Health, National Jewish Health, Denver, Colorado, USA., Hamzeh NY; Department of Medicine, University of Iowa, Iowa City, Iowa, USA nabeel-hamzeh@uiowa.edu.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2021 Nov 09; Vol. 11 (11), pp. e056841. Date of Electronic Publication: 2021 Nov 09.
DOI:	10.1136/bmjopen-2021-056841
Abstrakt:	Introduction: Sarcoidosis is a multiorgan granulomatous disorder thought to be triggered and influenced by gene-environment interactions. Sarcoidosis affects 45-300/100 000 individuals in the USA and has an increasing mortality rate. The greatest gap in knowledge about sarcoidosis pathobiology is a lack of understanding about the underlying immunological mechanisms driving progressive pulmonary disease. The objective of this study is to define the lung-specific and blood-specific longitudinal changes in the adaptive immune response and their relationship to progressive and non-progressive pulmonary outcomes in patients with recently diagnosed sarcoidosis. Methods and Analysis: The BRonchoscopy at Initial sarcoidosis diagnosis Targeting longitudinal Endpoints study is a US-based, NIH-sponsored longitudinal blood and bronchoscopy study. Enrolment will occur over four centres with a target sample size of 80 eligible participants within 18 months of tissue diagnosis. Participants will undergo six study visits over 18 months. In addition to serial measurement of lung function, symptom surveys and chest X-rays, participants will undergo collection of blood and two bronchoscopies with bronchoalveolar lavage separated by 6 months. Freshly processed samples will be stained and flow-sorted for isolation of CD4 +T helper (Th1, Th17.0 and Th17.1) and T regulatory cell immune populations, followed by next-generation RNA sequencing. We will construct bioinformatic tools using this gene expression to define sarcoidosis endotypes that associate with progressive and non-progressive pulmonary disease outcomes and validate the tools using an independent cohort. Ethics and Dissemination: The study protocol has been approved by the Institutional Review Boards at National Jewish Hospital (IRB# HS-3118), University of Iowa (IRB# 201801750), Johns Hopkins University (IRB# 00149513) and University of California, San Francisco (IRB# 17-23432). All participants will be required to provide written informed consent. Findings will be disseminated via journal publications, scientific conferences, patient advocacy group online content and social media platforms. Competing Interests: Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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