The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis.
The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis.
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DOI：
10.3389/fphar.2022.937490
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发表时间：
2022
影响因子：
5.6
通讯作者：
Du, Juan
中科院分区：
文献类型：
--
作者：
Lin, Lanmei;Wang, Yilun;Lu, Xiaonian;Wang, Tianxiao;Li, Qunyi;Wang, Runnan;Wu, Jinfeng;Xu, Jinhua;Du, Juan
银屑病是一种常见的免疫介导的炎症性皮肤病。虽然生物制剂治疗中重度银屑病取得了较好的临床疗效，但继发性无反应（SNR）现象也逐渐被认识。SNR是指患者使用TNF-α等生物制剂达到临床缓解后，疗效逐渐下降。阿维A作为一种免疫调节全身用药治疗银屑病，能提高患者对生物制剂的SNR，耐受性好，但疗效仍存在个体差异。许多相关炎性细胞因子的单核苷酸多态性（Single-nucleotide polymorphisms，SNPs）已被证明是银屑病药物反应个体差异的重要因素，但利用药物基因组学来减轻生物制剂的SNR的报道很少。本研究招募了43名银屑病患者和24名正常对照，以研究炎症细胞因子的SNP是否可以作为阿维A减轻银屑病患者对TNF-α生物制剂的SNR的生物标志物，包括rs 1800795（IL-6），rs6887695（IL-12 b），rs3212227（IL-12 b），rs 10484879（IL-17 a），rs4819554（IL-17 ra）、rs763780（IL-17 F）、rs11209032（IL 23 R）、rs11209026（IL 23 R）和rs2201841（IL 23 R）。该研究还分析了上述SNP与仅使用阿维A的患者的疗效之间的相关性，以了解改善是否归因于阿维A对SNR的干预或阿维A的简单反应。结果发现，在rs 112009032（IL-23 R）单核苷酸多态性纯合子AA患者中，阿维A可提高TNFα单克隆抗体的信噪比（χ2 = 6.577，p = 0.02）。TG基因型rs3212227（IL-12 B）患者对阿维A治疗更敏感（χ2 = 6.124，p = 0.035）。Rs3212227（χ2 = 7.664，p = 0.022）也与银屑病易感性相关。该研究可能为银屑病生物制剂继发性无效的个体化治疗提供临床决策参考。
Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.
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