在TNF途径的遗传变异影响TNFi响应在风湿性关节炎的混合人群
Pedro Augusto Silva Dos Santos Rodrigues1, Almirane Lima de Oliveira1, Katarina Mattos Brandão2
1Department of Bioregulation, Laboratory of Immunopharmacology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, Brazil.
Gene
|August 1, 2024
概括
在TNF途径的遗传变异影响类风湿性关节炎 (RA) 治疗反应,特别是用golimumab. 某些单核酸多态 (SNP) 与RA结果和安全相关,而不是诊断.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 类风湿病学 类风湿病学
背景情况:
- 风湿性关节炎 (RA) 是一种自身免疫性疾病,影响关节和生活质量.
- 瘤坏死因子 (TNF) 和介乐金6 (IL-6) 是RA病变和治疗中的关键细胞因子.
- TNF抑制剂 (TNFi) 用于RA,但有些患者缺乏反应或随着时间的推移而失去反应.
研究的目的:
- 调查TNF,TNFRSF1A和TNFRSF1B基因中的单核酸多态 (SNPs) 之间的关联以及RA诊断.
- 评估这些SNP之间的关系,RA临床结果和对TNFi治疗的反应.
- 在RA患者和健康对照者中分析TNF和IL-6的血清水平.
主要方法:
- 分析了来自654名受试者的临床,社会人口统计和遗传数据 (360名对照组,294名RA患者).
- 在TNF,TNFRSF1A和TNFRSF1B基因中SNP的基因定型.
- 在子样本中测量血清TNF和IL-6水平.
主要成果:
- 与对照组相比,在RA患者中观察到更高的TNF水平.
- 升高的IL-6水平与TNFi无反应有关,而响应者具有与对照组相似的水平.
- 在RA诊断中没有发现SNP关联,但rs767455-C与戈利穆马布的反应和较低的白细胞计数呈现出积极的关联.
结论:
- 特定的SNP (rs767455-C,rs1061622-G) 可能会影响TNFi反应,特别是对戈利马布,并影响免疫细胞计数和器官功能标志物.
- 这些多态性似乎与RA诊断无关.
- 需要进一步的大规模研究来证实TNF通路多态度对TNFi疗效和安全的影响.
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