Blood Gene Expression and Immune Cell Subtypes Associated with Chronic Obstructive Pulmonary Disease Exacerbations.
Blood Gene Expression and Immune Cell Subtypes Associated with Chronic Obstructive Pulmonary Disease Exacerbations.
复制标题
与慢性阻塞性肺疾病恶化相关的血液基因表达和免疫细胞亚型。
DOI：
10.1164/rccm.202301-0085oc
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发表时间：
2023
影响因子：
24.7
通讯作者：
Sin,D
中科院分区：
文献类型：
--
作者：
Ryu,MinHyung;Yun,JeongH;Morrow,JarrettD;Saferali,Aabida;Castaldi,Peter;Chase,Robert;Stav,Meryl;Xu,Zhonghui;Barjaktarevic,Igor;Han,MeiLan;Labaki,Wassim;Huang,YvonneJ;Christenson,Stephanie;O'Neal,Wanda;Bowler,Russell;Sin,D
依据：慢性阻塞性肺疾病急性加重（AE-COPD）与显著的疾病负担相关。血液免疫表型可以提高我们对COPD内型的认识，增加COPD急性加重的风险。Objective：To determine the relationship between transcriptome of circulating leukocytes and COPD acquisition.Methods：Blood RNA sequencing data（n= 3，618）from the COPDGene（Genetic Epidemiology of COPD）study进行了分析。使用来自ECLIPSE（纵向评估COPD以确定预测性替代终点）研究的血液微阵列数据（n= 646）进行验证。我们测试了血液基因表达与AE-COPD之间的关联。我们估算了白细胞亚型的丰度，并测试了它们与预期AE-COPD的相关性。在SPIROMICS（COPD研究中的亚群和中间结果）（n= 127）中对血液进行流式细胞术检测，并检测T细胞活化标志物与前瞻性AE-COPDs.Measurements和主要结果的相关性：COPD Gene（5.3 ± 1.7年）和ECLIPSE（3年）随访期间分别报告了4，030和2，368次急性加重。我们分别鉴定了890、675和3,217个与AE-COPD病史、持续性加重（每年至少一次加重）和预期加重率相关的基因。在COPDGene中，COPD患者（慢性阻塞性肺疾病全球倡议第2期）的预期急性加重次数与循环CD 8 +T细胞、CD 4 +T细胞和静息自然杀伤细胞呈负相关。与初始CD 4 +T细胞的负相关性在ECLIPSE中得到复制。在流式细胞术研究中，CTLA 4对CD 4 +T细胞的增加与AE-COPDs.Conclusions呈正相关：COPD患者循环淋巴细胞计数较低，特别是CD 4 +T细胞减少，更容易发生AE-COPDs，包括持续加重。
Rationale:Acute exacerbations of chronic obstructive pulmonary disease (AE-COPDs) are associated with a significant disease burden. Blood immune phenotyping may improve our understanding of a COPD endotype at increased risk of exacerbations.Objective:To determine the relationship between the transcriptome of circulating leukocytes and COPD exacerbations.Methods:Blood RNA sequencing data (n= 3,618) from the COPDGene (Genetic Epidemiology of COPD) study were analyzed. Blood microarray data (n= 646) from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study were used for validation. We tested the association between blood gene expression and AE-COPDs. We imputed the abundance of leukocyte subtypes and tested their association with prospective AE-COPDs. Flow cytometry was performed on blood in SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) (n= 127), and activation markers for T cells were tested for association with prospective AE-COPDs.Measurements and Main Results:Exacerbations were reported 4,030 and 2,368 times during follow-up in COPDGene (5.3 ± 1.7 yr) and ECLIPSE (3 yr), respectively. We identified 890, 675, and 3,217 genes associated with a history of AE-COPDs, persistent exacerbations (at least one exacerbation per year), and prospective exacerbation rate, respectively. In COPDGene, the number of prospective exacerbations in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage ⩾2) was negatively associated with circulating CD8+T cells, CD4+T cells, and resting natural killer cells. The negative association with naive CD4+T cells was replicated in ECLIPSE. In the flow-cytometry study, an increase in CTLA4 on CD4+T cells was positively associated with AE-COPDs.Conclusions:Individuals with COPD with lower circulating lymphocyte counts, particularly decreased CD4+T cells, are more susceptible to AE-COPDs, including persistent exacerbations.