基线血清和便微生物组生物标志物预测了Ulcerative Colitis中Ritlecitinib诱导疗法后的临床有效性和组织分子反应
Mina Hassan-Zahraee1, Zhan Ye1, Li Xi1
1Pfizer Inc, Cambridge, MA, USA.
血液和肠道微生物群中的生物标志物可以预测接受性结肠炎患者的治疗反应. 这些发现可能使性结肠炎 (UC) 的个性化药物成为可能.
科学领域:
- 胃肠道学和免疫学
- 药物基因组学和精准医学
背景情况:
- 利特利西替尼 (Ritlecitinib) 是一种口服的JAK3/TEC家族激酶抑制剂,在中度至重度的性结肠炎 (UC) 中显示出安全性和有效性.
- 识别预测生物标志物对于优化UC治疗策略至关重要.
研究的目的:
- 确定基线血清和微生物群标志物,预测瑞特利西提尼布在UC中的临床疗效.
- 开发非侵入性血清特征,作为利特莱西提尼布疗效的实时替代品.
主要方法:
- 使用蛋白质组学,转录组学和转基因组学分析周围血液和便样本,在8周的瑞特利西替尼治疗前后进行分析.
- 应用线性混合模型和后勤回归来识别预测性蛋白质标记物.
- 便元基因组学的差异表达分析,以区分响应者和非响应者.
主要成果:
- 四个基线血清标志物 (LTA,CCL21,HLA-E,MEGF10) 预测了临床缓解,内镜改善和组织学缓解.
- 在第8周,四种血清蛋白质 (IL4R,TNFRSF4,SPINK4,LAIR-1) 的变化预测了并发的内镜和组织学反应.
- 便转基因组学揭示了与临床和分子改善相关的基线和治疗反应标志.
结论:
- 血液和微生物组生物标志物有效地分层了UC中对ritlecitinib的反应.
- 这些生物标志物可能会促进UC治疗的精准医学方法.
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