检查Sjogren综合征临床异质性背后的生物学途径:蛋白质组和网络分析
Joe Scott Berry1, Jessica Tarn1, John Casement2
1Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Annals of the rheumatic diseases
|September 1, 2023
概括
这项研究使用蛋白质学识别了Sjogren综合征 (SS) 亚型背后的独特分子通路. 针对特定的途径,如对疲劳的IL-6,可以改善SS患者的治疗.
科学领域:
- 免疫学和风湿病学
- 蛋白质组学和网络生物学
- 系统生物学 系统生物学
背景情况:
- 斯乔格伦综合征 (SS) 呈现出显著的临床异质性,需要有效的分层方法.
- 之前的工作建立了纽卡斯尔Sjogren的分层工具 (NSST) 来识别四种不同的SS临床亚型.
- 了解这些亚型的分子基础对于开发向疗法至关重要.
研究的目的:
- 执行由NSST识别的SS亚型的蛋白质和网络分析.
- 阐明不同SS临床亚型的潜在病理生物学.
- 确定不同SS亚型的潜在治疗点.
主要方法:
- 使用O-link技术对180名SS受试者进行血清蛋白质分析 (5个面板中的454种独特蛋白质).
- 通过ARACNE算法重建网络,集成微分表达式数据.
- 重新分析一项III期托西利祖马布试验,根据NSST基线亚型对患者进行分层.
主要成果:
- 在SS亚型中鉴定出化学,细胞和TRIM21的差异表达.
- 参与能量代谢和氧化还原平衡的关键转录因子 (APE1/Ref-1,FOXO1,TIGAR,BACH1) 显示出差异性的表达.
- 基于NSST的分层显示,在托西利祖马布治疗后,高IL-6亚型的疲劳得分有所改善.
结论:
- 蛋白质组数据提供了有关驱动SS表现的途径的见解,并建议特定亚型的治疗点.
- 不同的分子网络与已识别的SS临床亚型相关.
- 需要进一步研究SS亚型中代谢变化和线粒体功能障碍.
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