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.
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.
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DOI：
10.1136/bmjopen-2021-056841
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发表时间：
2021-11-09
期刊：
影响因子：
2.9
通讯作者：
Hamzeh NY
中科院分区：
文献类型：
--
作者：
Koth LL;Harmacek LD;White EK;Arger NK;Powers L;Werner BR;Magallon RE;Grewal P;Barkes BQ;Li L;Gillespie M;Collins SE;Cardenas J;Chen ES;Maier LA;Leach SM;O'Connor BP;Hamzeh NY
结节病是一种多器官肉芽肿性疾病，被认为是由基因-环境相互作用引发和影响的。在美国，结节病影响到45-300/10万人，并且死亡率正在上升。关于结节病病理生物学知识的最大差距是缺乏对导致进行性肺部疾病的潜在免疫学机制的了解。本研究的目的是明确肺特异性和血液特异性适应性免疫反应的纵向变化，以及它们与新近诊断的结节病患者进展性和非进展性肺结局的关系。针对纵向终点的支气管镜检查最初诊断结节病研究是一项由美国国立卫生研究院赞助的纵向血液和支气管镜检查研究。将在组织诊断后18个月内招募四个中心，目标样本量为80名合格参与者。参与者将在18个月内进行6次考察访问。除了连续测量肺功能、症状调查和胸部X光外，参与者还将接受血液采集和两次支气管镜检查，并间隔6个 月进行支气管肺泡灌洗。新加工的样本将进行染色和流动分选，以分离出CD4+T辅助细胞(Th1、Th17.0和Th17.1)和T调节细胞免疫群体，然后进行下一代RNA测序。我们将构建生物信息学工具，使用该基因表达来定义与进行性和非进行性肺部疾病结局相关的结节病内型，并使用独立的队列来验证这些工具。该研究方案已得到国家犹太医院(IRB#HS-3118)、爱荷华大学(IRB#201801750)、约翰霍普金斯大学(IRB#00149513)和加州大学旧金山分校(IRB#17-23432)的机构审查委员会的批准。所有参与者将被要求提供书面知情同意。研究结果将通过期刊出版物、科学会议、患者权益倡导团体在线内容和社交媒体平台传播。
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. 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. 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.
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DOI：
10.1111/j.1749-6632.1986.tb18540.x
发表时间：
1986-06-06
影响因子：
5.2
作者：
BRESNITZ, EA;STOLLEY, PD;SOPER, K
通讯作者：
SOPER, K
影响因子：
24.3
作者：
Kaiser, Ylva;Lepzien, Rico;Grunewald, Johan
通讯作者：
Grunewald, Johan
DOI：
10.1164/rccm.202002-0251st
发表时间：
2020-04-15
影响因子：
24.7
作者：
Crouser, Elliott D.;Maier, Lisa A.;Baughman, Robert P.
通讯作者：
Baughman, Robert P.
DOI：
10.1164/rccm.200211-1311oc
发表时间：
2003-09-01
影响因子：
24.7
作者：
Collard, HR;King, TE;Brown, KK
通讯作者：
Brown, KK
影响因子：
9.6
作者：
Grutters, JC;Fellrath, JM;van Velzen-Blad, H
通讯作者：
van Velzen-Blad, H