Abstract
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.
Highlights
Vitiligo is an acquired depigmentation skin disorder that affects 0.5%–2% of world’s population [1]
Several clinical parameters have been associated with more favorable response to vitiligo repigmentation therapies, including pediatric age, facial location, short disease duration, and absence of leukotrichia [48, 49]
Since our study focused on patients with target lesions without leukotrichia that are mostly from torso and proximal extremities, our study was not designed to evaluate the impact of location on facial or acral sites, or leukotrichia on therapeutic responses
Summary
Vitiligo is an acquired depigmentation skin disorder that affects 0.5%–2% of world’s population [1]. Patients with vitiligo develop white patches on their skin, including in visible areas such as the face, neck, hands, and forearms. Two major types of vitiligo are recognized: segmental vitiligo (SV), which affects a localized asymmetrical area of the body, and nonsegmental vitiligo (NSV), the more common subtype, which often involves multiple body sites in a symmetrical fashion. The pathogenesis of vitiligo is unknown, previous studies identified multiple factors that are potentially involved in the development of vitiligo, including genetic predisposition (such as polymorphisms in genes involved in the immune response and in melanogenesis) [8,9,10,11,12,13,14], inducible heat shock protein 70 [15, 16], activation in vitiligo lesions of adaptive immunity [such as CXCL10 [17]] and innate immunity [such as NK cells [18]], environmental factors
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