Abstract:
Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies.
摘要:
类风湿性关节炎(RA)是一种多因素的自身免疫性炎性疾病,主要影响关节,降低功能能力和影响生活质量。细胞因子如肿瘤坏死因子(TNF)和白细胞介素6(IL-6)在该疾病的发病机制和治疗中至关重要。一些使用TNF抑制剂(TNFi)的患者对这些药物没有反应或失去反应。临床,社会人口统计学,和遗传数据用于评估TNF的单核苷酸多态性(SNP)的关联,TNFRSF1A,和TNFRSF1B基因与RA的诊断,标准化评分结果,实验室测试,和对TNFi的反应。在一个子样本中,检测血清细胞因子TNF和IL-6水平。总共654名受试者(360名健康对照和294名诊断为RA)被包括在分析中。在诊断为RA的个体中发现较高水平的TNF。对TNFi治疗无反应的个体中IL-6水平较高,而反应者的水平与没有疾病的水平相当。研究的SNP与RA的诊断之间没有发现关联;然而,rs767455-C似乎在戈利木单抗治疗的反应中起作用,与更好的治疗反应和较低的平均血清白细胞水平有关。此外,rs1061622-G与较差的功能能力相关,rs1800629-A与较高的白细胞值和血清转氨酶水平相关。rs1061622-G和rs767455-C可能在对TNFi治疗的反应中起作用,特别是对于使用戈利木单抗的患者,尽管它们似乎与RA的诊断无关。TNF通路中的多态性可能会影响RA患者免疫细胞的基线水平以及肾功能和肝功能标志物。我们的研究结果强调了评估这些多态性对TNFi反应和安全性的影响的重要性。特别是在大规模研究中。