基线外周血液单核细胞转录在乌斯特基努马布治疗前与克罗恩氏病临床反应1年相关
Maya Granot1, Tzipi Braun1, Gilat Efroni1
1Pediatric Gastroenterology and Nutrition Unit, Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel-Aviv, Israel.
预测克罗恩氏病对乌斯特基努马布的反应是具有挑战性的. 非响应者显示炎症基因表达增加,特别是与细胞因子活性和髓状细胞相关,这表明治疗结果的潜在生物标志物.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 基因组学就是基因组学.
背景情况:
- 乌斯特基努马布是一种生物向IL-12/23的药物,可治疗克罗恩氏病 (CD),缓解率约为50%.
- 预测患者对乌斯特基努马布的反应对于优化治疗策略至关重要.
研究的目的:
- 为了确定基线外周血液基因表达预测者对CD患者的 ustekinumab 临床反应的临床反应.
- 研究ustekinumab响应者和不响应者之间的转录组差异.
主要方法:
- 在 ustekinumab 开始治疗之前,从 36 名 CD 患者的外周血液单核细胞的 RNA 测序.
- 使用DESeq2进行差异基因表达分析,使用ToppGene进行功能丰富分析.
主要成果:
- 在FDR校正后,没有显著的基因表达特征区分了响应者和非响应者.
- 然而,68个基因,包括CXCL1/2/3,在非响应者中被上调 (P<0.05,折叠变化>1.5).
- 丰富分析揭示了与细胞因子活性,化学因子受体结合,IL-10信号传递和非响应者的髓状细胞特征相关的途径.
结论:
- 基线外周血液转录组没有显示出CD中乌斯特基努马布反应的明确预测特征.
- 没有反应的人表现出增强的炎症特征,这表明了需要进一步研究的潜在生物标志物.
- 需要更大的队列来验证这些初步发现并探索它们的临床实用性.
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