University of Dundee, College of Medicine, Dentistry, and Nursing, Dundee, UK.
Department of Dermatology and Photobiology, Ninewells Hospital, Dundee, UK.
Clin Exp Dermatol. 2017 Aug;42(6):651-655. doi: 10.1111/ced.13100. Epub 2017 May 17.
It is well documented that patients with human leucocyte antigen (HLA)-Cw6+ (type 1) psoriasis have increased severity and reduced age of onset of psoriasis. However, not much is known about any differential response of this genetic subgroup to various treatments. We set out to determine if there was any genetic association of the HLA-Cw6 allele with the first-line systemic treatment commonly used in psoriasis, methotrexate. A cohort of patients from Tayside in Scotland was recruited through a novel generic consenting process (GoShare); they were extensively phenotyped and analysed for an association of their HLA-Cw6 genotype status with treatment outcomes. HLA-Cw6+ patients showed notably improved response to methotrexate (P = 0.05), and further analysis demonstrated an even greater response in a subcohort of the HLA-Cw6+ patients, who did not have concomitant psoriatic arthritis (P = 0.01). HLA-Cw6+ patients also exhibited fewer treatment-limiting adverse events. In addition to these findings, the methodology and primary clinical outcome phenotype, which we validate here, will greatly facilitate replication of the present results in independent cohorts.
已有大量文献记载，人类白细胞抗原（HLA）-Cw6+（1 型）银屑病患者的银屑病严重程度更高，发病年龄更小。然而，对于这一遗传亚组对各种治疗方法的不同反应，人们知之甚少。我们着手确定 HLA-Cw6 等位基因是否与银屑病的一线系统治疗药物——甲氨蝶呤存在遗传关联。我们通过一种新颖的通用同意程序（GoShare）在苏格兰泰赛德地区招募了一组患者；对他们进行了广泛的表型分析，并分析了他们的 HLA-Cw6 基因型与治疗结果之间的关联。HLA-Cw6+患者对甲氨蝶呤的反应明显改善（P=0.05），进一步的分析表明，在 HLA-Cw6+患者亚组中，那些没有同时患有银屑病关节炎的患者反应更为显著（P=0.01）。HLA-Cw6+患者出现的治疗限制不良事件也较少。除了这些发现，我们在这里验证的方法和主要临床结果表型将极大地促进在独立队列中复制本研究结果。
