通过结核病治疗与糖尿病并发症的血液转录组的破解受损
Clare Eckold1, Cassandra L R van Doorn2, Rovina Ruslami3
1Department of Infection Biology and TB Centre, London School of Hygiene & Tropical Medicine, London, UK.
Clinical and translational medicine
|August 31, 2023
概括
糖尿病和结核病 (TB-DM) 患者在结核病治疗期间表现出长时间的炎症基因表达变化. 这些差异在治疗后仍然存在,影响结核病的结果,并表明需要量身定制的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 传染性疾病 传染性疾病
背景情况:
- 糖尿病显著增加结核病 (TB) 的风险,并使治疗结果恶化.
- 以前的研究表明,结核病-糖尿病 (TB-DM) 患者在诊断时的炎症增加和干扰素反应减少.
- 在整个结核病治疗过程中,这些转录组变化的持久性仍然不清楚.
研究的目的:
- 调查结核病治疗期间,TB-DM中鲜明的血液转录组概况是否在结核病治疗期间持续存在.
- 确定这些持续变化是否有助于TB治疗的不良结果.
- 在不同临床群体中开发结核病治疗反应的预测模型.
主要方法:
- 肺结核患者根据HbA1c水平被分为TB-DM,糖尿病前期,与结核相关的高血糖症或仅结核的组.
- 使用RNA-Seq和在诊断和整个治疗期间的向测试分析了血液基因表达.
- 使用纵向混合模型回归来分析群体之间的依赖时间的基因表达差异.
主要成果:
- 在诊断时观察到结核病和TB-DM患者之间基因表达的显著差异,并在整个治疗过程中持续存在.
- 在治疗期间,与先天免疫,抗微生物反应和炎症相关的基因在TB-DM患者中被上调.
- 尽管存在差异,但治疗期间转录组变化的整体模式在不同组中是相似的,这使得预测模型的开发成为可能.
结论:
- 结核病-DM患者的恶化的转录组变化在结核病治疗期间缓慢消失,与未复杂的结核病患者在治疗后保持区别.
- 在TB-DM中,这种延长的炎症反应可能需要延长治疗时间或宿主导疗法.
- 未来的基于转录基因组的结核病治疗反应生物标志物应纳入糖尿病患者的数据,以获得更广泛的应用.
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