JAMA Dermatol. 2013 Sep;149(9):1033-9. doi: 10.1001/jamadermatol.2013.4632.
Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti–tumor necrosis factor (TNF) treatment of psoriasis.
To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis.
Retrospective series of patients with psoriasis who received anti-TNF therapy(infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks.
Two psoriasis referral centers.
Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents.
Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping.
The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes.
Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity alleles may contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF.
Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.
参与生物治疗免疫途径的蛋白编码基因的变异性可能解释了抗肿瘤坏死因子（TNF）治疗银屑病的结果差异。
评估 2 种 Fcγ 受体（FcγR）多态性在银屑病抗 TNF 治疗反应中的作用。
回顾性系列病例，纳入 2007 年 1 月 1 日至 2010 年 12 月 31 日期间接受抗 TNF 治疗（英夫利昔单抗、阿达木单抗或依那西普）的银屑病患者。患者接受了 12 周的随访。
两个银屑病转诊中心。
70 名初治的中重度银屑病患者接受了抗 TNF 药物治疗。
患者进行了 FcγRIIA-H131R 和 FcγRIIIA-V158F 多态性基因分型。
在基线时以及治疗的第 6-8 周和第 12 周评估银屑病面积和严重程度指数（PASI）和体表面积。将多态基因型与治疗结果相关联。
双变量分析显示，FcγR 低亲和力基因型与治疗结束时 PASI 和体表面积的改善之间无显著相关性。相反，携带高亲和力等位基因的患者在中间点的体表面积减少更大，这在多变量分析中仍然是独立的。我们还在多变量分析中检测到这两种多态性的累加效应。高亲和力等位基因可能有助于更快的反应，因为更有效地清除表达 TNF 的相关细胞。
这项关于银屑病 FcγR 及生物治疗药物遗传学的初步研究结果表明，FcγRIIA-H131R 和 FcγRIIIA-V158F 多态性在抗 TNF 治疗银屑病的结果中具有临床意义。这些结果可能有助于皮肤科医生指导治疗决策，特别是在需要快速反应的非常严重的情况下。
