免疫基因相关性网络区分慢性肺异位移植功能障碍和生存
Kaveh Moghbeli1, Iulia Popescu1, Carlo J Iasella2
1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15213, USA.
概括
研究人员在呼吸道转录组中确定了关键的免疫通路,与肺移植受体的慢性肺异位功能障碍 (CLAD) 有关. 这些发现为CLAD和新的治疗点提供了潜在的分子诊断.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 移植医学 移植医学
背景情况:
- 慢性肺异位移植功能障碍 (CLAD) 显著限制了肺移植接受者 (LTRs) 的长期生存率.
- 目前,CLAD是一种排除诊断,治疗选择有限.
- 分子诊断对于风险分层和确定CLAD的新疗法目标至关重要.
研究的目的:
- 通过呼吸道转录组分析识别与CLAD相关的免疫路径和分子标记物.
- 发现潜在的CLAD诊断和预后生物标志物.
主要方法:
- 权重基因相关联网络分析 (WGCNA) 应用于来自CLAD和稳定的LTR的LTR的气道刷毛的RNA-seq数据.
- 基因共同表达网络 (模块) 分析了它们与CLAD的关联,其严重程度和患者存活率.
- 下游蛋白质和eicosanoid水平在支气管支气管洗中测量,结果在外部队列中得到验证.
主要成果:
- 三个基因模块与CLAD正相关,其严重程度,移植功能障碍和存活率,为急性阶段反应,1型自适应免疫和先天免疫通路进行了丰富.
- 第四个模块显示了保护作用,与与CLAD相关的模块相反相关.
- 在外部验证队列中,模块表达成功地将LTR与CLAD区分开来,并与较差的生存率相关联.
结论:
- 在CLAD中,呼吸道转录组的特征是与免疫反应相关的共同表达网络.
- 这些已识别的网络模块作为CLAD预后和治疗向的潜在分子生物标志物.
- 这项研究为开发分子诊断提供了基础,以改善肺移植接受者的结果.
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