哮喘联盟

   摘要
   背景：肥大细胞（MCs）和嗜碱性粒细胞在哮喘的病理生理中起着重要作用，然而直接检测很困难，并且对严重哮喘的临床和炎症相关性了解甚少。MCs /嗜碱性粒细胞的转录组学特征可能允许使用基因表达测定其在痰液中的表达。建立并验证痰中MC /嗜碱性粒细胞基因特征，探讨其与重症哮喘炎症及临床特征的关系。
   方法：在痰液微阵列中筛选134个MC /嗜碱性粒细胞候选基因（由免疫基因组计划联合会鉴定），以比较对照组（n = 18）、嗜酸性粒细胞性哮喘（n=29）和非嗜酸性粒细胞性哮喘（n=30）之间的差异表达。在一个单独的哮喘队列（n=20）中，通过流式细胞术定量分析痰中MCs和嗜碱性粒细胞，确认基因表达的相关性，验证候选基因。在一个严重哮喘队列（n=81）中检测经验证的基因特征，并测试炎症和临床相关性。
   结果：通过基因芯片筛选和验证，我们发现与痰中MCs/嗜碱性粒细胞相关的8个靶点的qPCR基因表达：TPSAB1/TPSB2、CPA3、ENO2、GATA2、KIT、GPR56、HDC、SOCS2。在重症哮喘中，MC/嗜碱性粒细胞基因与嗜酸性气道炎症（GATA2、TPSB2、CPA3、GPR56、HDC、SOCS2）、血嗜酸性粒细胞（TPSB2、CPA3、GATA2、SOCS2、FCER1A、HDC）、FeNO（GATA2、SOCS2）、肺功能下降（KIT、ENO2）和中度加重史（GATA2、SOCS2）相关。
   结论：在重症哮喘中，以qPCR为基础的测量反映了不同的痰MC/嗜碱性粒细胞丰度，表明MCs/嗜碱性粒细胞与嗜酸性粒细胞炎症、肺活量测定和加重史相关。
 

(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)

(J Allergy Clin Immunol. 2021 Feb 18;S0091-6749(21)00222-0. doi: 10.1016/j.jaci.2021.01.033.)

 

Sputum mast cell/basophil gene expression relates to inflammatory and clinical features of severe asthma

Natasha A Winter, Ling Qin, Peter G Gibson, Vanessa M Mcdonald, Katherine J Baines, Jack Faulkner, Tiffany-Jane Evans, Michael Fricker

Abstract
BACKGROUND:Mast cells (MCs) and basophils are important in asthma pathophysiology, however direct measurement is difficult, and clinical and inflammatory associations in severe asthma are poorly understood. Transcriptomic hallmarks of MCs/basophils may allow their measurement in sputum using gene expression. Develop and validate a sputum MC/basophil gene signature and investigate its relationship to inflammatory and clinical characteristics of severe asthma.
METHODS:134 candidate MC/basophil genes (identified by the Immunological Genome Project Consortium) were screened in sputum microarray for differential expression between controls (n=18), eosinophilic (n=29) and non-eosinophilic asthma (n=30). Candidate genes were validated by confirming correlation of gene expression with flow cytometry-quantified sputum MCs and basophils in a separate asthma cohort (n=20). The validated gene signature was measured in a severe asthma cohort (n=81), and inflammatory and clinical associations tested.
RESULTS:Through microarray screening and subsequent validation, we found qPCR gene expression of 8 targets correlated with sputum MCs/basophils: TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2. In severe asthma, MC/basophil genes were associated with eosinophilic airway inflammation (GATA2, TPSB2, CPA3, GPR56, HDC, SOCS2), blood eosinophils (TPSB2, CPA3, GATA2, SOCS2, FCER1A, HDC), FeNO (GATA2, SOCS2), decreased lung function (KIT, ENO2) and moderate exacerbation history (GATA2, SOCS2).
CONCLUSION:qPCR-based measures reflect varying sputum MC/basophil abundance, demonstrating associations of MCs/basophils with eosinophilic inflammation, spirometry and exacerbation history in severe asthma.