Department of Bioregulation, Laboratory of Immunopharmacology and Molecular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, Brazil.
Department of Medicine, School of Pharmacy, Federal University of Bahia, Salvador, Bahia, Brazil.
Gene. 2024 Nov 30;928:148804. doi: 10.1016/j.gene.2024.148804. Epub 2024 Jul 30.
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.
类风湿关节炎（RA）是一种多因素自身免疫性炎症性疾病，主要影响关节，降低功能能力并影响生活质量。肿瘤坏死因子（TNF）和白细胞介素 6（IL-6）等细胞因子在这种疾病的发病机制和治疗中起着至关重要的作用。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。本研究采用临床、社会人口统计学和遗传数据，评估 TNF、TNFRSF1A 和 TNFRSF1B 基因的单核苷酸多态性（SNP）与 RA 的诊断、标准化评分结果、实验室检查以及对 TNFi 的反应之间的相关性。在一个亚样本中，对 TNF 和 IL-6 血清细胞因子水平进行了检测。共纳入 654 名受试者（360 名健康对照和 294 名确诊为 RA 的患者）进行分析。与未接受 TNFi 治疗的个体相比，诊断为 RA 的个体 TNF 水平更高。未应答者的 IL-6 水平更高，而应答者的水平与无疾病者相当。研究中未发现 SNP 与 RA 诊断之间存在相关性；然而，rs767455-C 似乎在对戈利木单抗治疗的反应中发挥作用，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 TNFi 治疗反应中发挥作用，特别是对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 患者免疫细胞和肾功能、肝功能标志物的基线水平。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，特别是在更大规模的研究中。
