National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, Taiwan.
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Mol Diagn Ther. 2022 Sep;26(5):541-549. doi: 10.1007/s40291-022-00603-4. Epub 2022 Jul 5.
Psoriasis is a chronic inflammatory disease with a strong genetic background, particularly the human leukocyte antigen (HLA). HLA-Cw6 has been shown to be the major disease susceptibility locus and affects the phenotypes and treatment response in psoriasis; however, the prevalence of HLA-Cw6 is far lower than HLA-Cw1 in some Asian countries.
The aim of this study was to determine whether HLA-Cw1 predisposes psoriasis patients to different treatment responses of biologics and other systemic therapy.
This retrospective case-control study included 126 patients with moderate to severe plaque-type psoriasis who had been genotyped and treated in a special psoriasis clinic. HLA-Cw1-positive and -negative patients were compared.
Our results showed that HLA-Cw1-negative patients were significantly more likely to respond (achieve Psoriasis Area and Severity Index [PASI] 75 after a 12- to 16-week treatment course) to biologics (including etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; odds ratio [OR] 1.99, 95% confidence interval [CI] 1.17-3.44, p = 0.0122) and especially to ustekinumab (OR 3.27, 95% CI 1.03-11.30; p = 0.0496). An HLA-Cw1 allele dose effect was also found. The results remained after multivariate logistic regression analysis. HLA-Cw1-negative patients also showed significantly greater improvement of PASI in ustekinumab and biologics (p = 0.0044 and p = 0.0064, respectively), with other biologics showing non-significant trends. HLA-Cw1 status did not affect the treatment responses of non-biologic systemic treatment, including phototherapy.
There is an association between HLA-Cw1 and treatment response to biologics, but not to non-biologics, in our Asian population of patients with moderate to severe psoriasis; however, the exact mechanism and role of HLA-Cw1 remain to be investigated.
银屑病是一种具有强烈遗传背景的慢性炎症性疾病，特别是人类白细胞抗原（HLA）。已经表明 HLA-Cw6 是主要的疾病易感基因座，并且影响银屑病的表型和治疗反应；然而，在一些亚洲国家，HLA-Cw6 的患病率远低于 HLA-Cw1。
本研究旨在确定 HLA-Cw1 是否使银屑病患者对生物制剂和其他全身治疗的不同治疗反应具有倾向性。
这是一项回顾性病例对照研究，纳入了在专门的银屑病诊所接受基因分型和治疗的 126 例中重度斑块型银屑病患者。比较了 HLA-Cw1 阳性和阴性患者。
我们的结果表明，HLA-Cw1 阴性患者对生物制剂（包括依那西普、阿达木单抗、乌司奴单抗、司库奇尤单抗、依奇珠单抗和古塞库单抗）的治疗反应（在 12-16 周的治疗过程中达到银屑病面积和严重程度指数 [PASI]75）显著更高（比值比 [OR]1.99，95%置信区间 [CI]1.17-3.44，p=0.0122），尤其是乌司奴单抗（OR 3.27，95%CI 1.03-11.30；p=0.0496）。还发现了 HLA-Cw1 等位基因剂量效应。多变量逻辑回归分析后结果仍然成立。HLA-Cw1 阴性患者在乌司奴单抗和生物制剂治疗中也显示出 PASI 显著更大的改善（p=0.0044 和 p=0.0064），而其他生物制剂则显示出非显著趋势。HLA-Cw1 状态并不影响非生物制剂全身治疗的治疗反应，包括光疗。
在我们的亚洲中重度银屑病患者群体中，HLA-Cw1 与生物制剂治疗反应相关，但与非生物制剂无关；然而，HLA-Cw1 的确切机制和作用仍有待研究。
