Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Front Immunol. 2021 Mar 5;12:613031. doi: 10.3389/fimmu.2021.613031. eCollection 2021.
Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients' responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient's response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving > 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future.
白癜风是一种获得性色素减退性皮肤病,由免疫介导的黑素细胞死亡引起。白癜风最常见的治疗方法是窄带紫外线 B 光疗,通常与他克莫司等局部治疗联合使用。然而,患者对这些治疗的反应差异很大。迄今为止,这种异质性的机制尚不清楚,也没有可以预测个体患者对治疗反应的分子指标。本研究的目的是确定与白癜风对治疗反应相关的临床参数和基因表达生物标志物。6 例节段性白癜风患者和 30 例非节段性白癜风患者在接受联合 UBUVB 和他克莫司治疗 6 个月前,对病变和非病变皮肤进行了转录组测序,并根据靶病变达到>10%复色与否,将其分为良好反应组和不良反应组。我们的研究表明,治疗反应性白癜风病变的疾病持续时间明显短于非反应性白癜风病变(2.5 年 vs 11.5 年,p=0.046,t-检验),而在年龄、性别、种族、白癜风亚型或疾病严重程度方面无显著差异。转录组分析确定了一组 68 个基因,可将良好反应与不良反应病变区分开来,包括免疫活性基因的上调,如 CXCL10、FCRL3 和 TCR 等。此外,与疾病持续时间长的白癜风病变相比,疾病持续时间短的病变也具有更高水平的免疫活性基因表达,包括一些(如 FCRL3 和 TCR 基因)与良好的治疗反应相关。总之,本研究确定了与免疫抑制性 NBUVB+tacrolimus 治疗的良好反应相关的临床参数和一组免疫活性和其他基因表达生物标志物。这些标志物在未来可能对白癜风患者的个体化治疗管理具有临床应用价值。