Department of Physiology, University of Medicine and Pharmacy Iuliu Hatieganu, 400347 Cluj-Napoca, Romania.
Department of Pathophysiology, University of Medicine and Pharmacy Iuliu Hatieganu, 400347 Cluj-Napoca, Romania.
Genes (Basel). 2023 May 22;14(5):1123. doi: 10.3390/genes14051123.
Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.
银屑病是一种系统性炎症性疾病，与多种合并症相关。它涉及环境因素和多基因易感性之间的复杂相互作用。IL-17 家族是银屑病发病机制的主要参与者之一。继发性无应答很常见，尤其是在长期使用 TNF-α 抑制剂时，但即使是新型生物制剂，如 IL-17 抑制剂，也不罕见。鉴定治疗效果和安全性的临床有用生物标志物将能够优化治疗选择，提高患者的生活质量和结局，并降低医疗保健成本。据我们所知，这是第一项评估罗马尼亚和东南欧生物初治和继发性无应答银屑病患者中 IL-17F(rs763780)和 IL-17RA(rs4819554)基因遗传多态性与生物治疗反应和其他临床数据之间关系的研究。我们对 81 名诊断为中重度慢性斑块型银屑病且首次接受生物治疗的患者进行了前瞻性、纵向、分析性队列研究。在接受 TNF-α 抑制剂治疗的 79 名患者中，有 44 名出现继发性无应答。所有患者均对 IL-17F 和 IL-17RA 基因的两个 SNP 进行了基因分型。IL-17F 基因中的 rs763780 多态性可能是预测哪些患者对抗 TNF-α 治疗有反应的有吸引力的候选生物标志物。另一个新兴的 IL-17RA 基因中的 rs4819554 与指甲银屑病风险和中重度斑块型银屑病患者较高 BMI 之间的关联也被描述。
