Autoimmune Destruction Of Melanocytes Research Articles

543 - Early repigmentation of stable vitiligo through point-of-care melanocyte transfer using non-cultured autologous skin cell suspension

Abstract Introduction Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1–3 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).4 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. Objective The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.

Early Repigmentation of Stable Vitiligo through Point-of-Care Melanocyte Transfer Using Non-Cultured Autologous Skin Cell Suspension

Introduction: Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1,2 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).3 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods: A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results: A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion: A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.

ViCEKb: Vitiligo-linked Chemical Exposome Knowledgebase

Vitiligo is a complex disease wherein the environmental factors, in conjunction with the underlying genetic predispositions, trigger the autoimmune destruction of melanocytes, ultimately leading to depigmented patches on the skin. While genetic factors have been extensively studied, the knowledge on environmental triggers remains sparse and less understood. To address this knowledge gap, we present the first comprehensive knowledgebase of vitiligo-triggering chemicals namely, Vitiligo-linked Chemical Exposome Knowledgebase (ViCEKb). ViCEKb involves an extensive and systematic manual effort in curation of published literature and subsequent compilation of 113 unique chemical triggers of vitiligo. ViCEKb standardizes various chemical information, and categorizes the chemicals based on their evidences and sources of exposure. Importantly, ViCEKb contains a wide range of metrics necessary for different toxicological evaluations. Notably, we observed that ViCEKb chemicals are present in a variety of consumer products. For instance, Propyl gallate is present as a fragrance substance in various household products, and Flutamide is used in medication to treat prostate cancer. These two chemicals have the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Furthermore, an extensive cheminformatics-based investigation revealed that ViCEKb chemical space is structurally diverse and comprises unique chemical scaffolds in comparison with skin specific regulatory lists. For example, Neomycin and 2,3,5-Triglycidyl-4-aminophenol have unique chemical scaffolds and the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Finally, a transcriptomics-based analysis of ViCEKb chemical perturbations in skin cell samples highlighted the commonality in their linked biological processes. Overall, we present the first comprehensive effort in compilation and exploration of various chemical triggers of vitiligo. We believe such a resource will enable in deciphering the complex etiology of vitiligo and aid in the characterization of human chemical exposome. ViCEKb is freely available for academic research at: https://cb.imsc.res.in/vicekb.

Evaluation of Serum Level of Interleukin 15 in Active Vitiligo Compared to Stable Disease and Healthy Control

Abstract Background Vitiligo is a common acquired disorder of depigmentation. Its pathogenesis entails a T helper (TH) 1-cytotoxic T (CT) lymphocytes mediated autoimmune melanocyte destruction. Interleukin (IL)-15 is one of the IL-2 family of cytokines and shares several actions with IL-2. IL-15 enhances survival, maturation, and functional activity of natural killer, neutrophils, and dendritic cells. Furthermore, it potentiates survival, maturation, and cytotoxicity of memory CT cells. IL-15 has been shown to play a crucial role in the pathogenesis of several autoimmune diseases but was poorly investigated in patients with vitiligo. Aims To investigate the role of IL-15 in the pathogenesis of vitiligo. Patients and Methods In total, 40 Patients with vitiligo and 20 controls matched for age and gender were enrolled in the study. Vitiligo Extent Score (VES) and Vitiligo Disease Activity (VIDA) score were used to assess vitiligo severity and activity, respectively. Serum level of IL-15 was assessed by enzyme-linked immune-sorbent assay. Results Serum IL-15 level, in patients with vitiligo, was significantly higher in comparison with the control group (P =. 001). A significant positive correlation was found between serum IL-15 level and VES score (P =. 001) Conclusion IL-15 level was elevated in the sera of patients with vitiligo. IL-15 may therefore have a significant impact on vitiligo autoimmune pathogenesis, and further identification of its molecular roles may highlight new therapeutic strategies for vitiligo.

Altered Levels of Negative Costimulatory Molecule V-Set Domain-Containing T-Cell Activation Inhibitor-1 (VTCN1) and Metalloprotease Nardilysin (NRD1) are Associated with Generalized Active Vitiligo

ABSTRACT Background Vitiligo is characterized by depigmented macules on the skin caused due to autoimmune destruction of melanocytes. V-set domain-containing T-cell activation inhibitor-1 (VTCN1) is a negative costimulatory molecule that plays a vital role in suppressing autoimmunity and tuning immune response. Nardilysin (NRD1), a metalloproteinase, cleaves membrane-tethered VTCN1 resulting in the shedding of soluble-VTCN1 (sVTCN1). However, the role of VTCN1 and NRD1 in vitiligo pathogenesis is unexplored. Objectives and methods This study was aimed to (i) Investigate the association of VTCN1 intronic polymorphisms (rs10923223 T/C and rs12046117 C/T) with vitiligo susceptibility in Gujarat population by using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) (ii) Estimate VTCN1 & NRD1 transcript levels from peripheral blood mononuclear cells (PBMCs) and skin samples of vitiligo patients by real-time PCR, (iii) Estimate sVTCN1 and NRD1 protein levels from plasma by ELISA and (iv) Estimate VTCN1 protein levels in the skin samples of vitiligo patients by immunofluorescence. Results The analysis revealed increased VTCN1 and NRD1 transcript levels in the skin (p = .039, p = .021 respectively), increased sVTCN1 and NRD1 levels (p = .026, p = .015 respectively) in the plasma, and decreased VTCN1 protein levels (p = .0002) in the skin of vitiligo patients as compared to healthy controls. The genetic analysis revealed no significant association of VTCN1 intronic polymorphisms rs10923223 T/C and rs12046117 C/T with vitiligo susceptibility in Gujarat population (p = .359, p = .937, respectively). Conclusions The present study revealed altered VTCN1 and NRD1 expressions in the blood and skin of vitiligo patients, suggesting their potential role in the development and progression of Vitiligo.

Radiotherapy-induced vitiligo: A systematic review of patient demographics and clinical characteristics of vitiligo following radiation therapy

To the Editor: Vitiligo is characterized by depigmentation of the skin and hair because of autoimmune destruction of melanocytes.1 The etiology of vitiligo is multifactorial and may include some forms of radiation therapy, such as external beam radiation therapy.2 The current literature lacks a cohesive summary of the clinical characteristics of radiotherapy-induced vitiligo. Our purpose was to conduct a systematic review of the patient demographics and clinical characteristics of radiotherapy-induced vitiligo.

Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo.

Vitiligo is a common dermatological disorder affecting 1–2% of the world’s population. It is characterized by postnatal, autoimmune destructions of melanocytes in the skin, resulting in patches of depigmentation. Autoimmunity in vitiligo may also affect melanocytes in non-integumental tissues, including the eyes where choroidal melanocytes are the target of the autoimmune response. The Smyth line (SL) of chicken is the only animal model that spontaneously and predictably develops all clinical and biological manifestations of autoimmune vitiligo. In SL vitiligo (SLV), destruction of epidermal melanocytes in growing feathers (GFs) involves a melanocyte-specific, Th1-mediated cellular immune response. Smyth chickens may also exhibit uveitis and vision impairment. Previous studies established a strong association between SLV and vision impairment, including similar pathology in affected eyes and GFs. To determine the presence, types, and activities of choroid infiltrating mononuclear cells, we collected eyes before, near onset, and during active SLV from sighted, partially blind, and blind SL chickens. All SL chickens with vision impairment had SLV. Immunohistochemistry and quantitative reverse transcriptase-PCR analyses revealed mononuclear cell and cytokine expression profiles in the autoimmune destruction of melanocytes in choroids that are identical to those described in GF, demonstrating the systemic nature of autoimmunity against melanocytes in SLV. In addition, we observed aberrant melanogenesis in SL eyes. The immunopathogenesis in SL vision impairment resembles human vitiligo-associated ocular diseases, especially Vogt–Koyanagi–Harada syndrome and sympathetic ophthalmia. Hence, the Smyth chicken autoimmune vitiligo model provides the opportunity to expand our understanding of spontaneous autoimmune pigmentation disorders and to develop effective treatment strategies.

MicroRNA-637 Relieves Oxidative Damage in Human Melanocytes Through Down-Regulating Transient Receptor Potential Melastatin 2 Expression

Background: Vitiligo, a chronic, autoimmune destruction of melanocytes, caused by the disappearance of epidermal melanocytes, but the mechanism is not fully understood. Although emerging evidence demonstrated that abnormal regulation of microRNAs (miRNAs) were associated with the pathogenesis of diseases, the functions of miR-637 in vitiligo remain unclear. Objective: This research was designed to explore the potential roles of miR-637 in hydrogen peroxide (H2O2)-induced human primary melanocytes in vitiligo. Methods: Human primary melanocytes were induced by 250 μmol/L H2O2 for 4 h to establish oxidative injury of melanocytes model. Cell viability and apoptosis analyzed by MTT and flow cytometry assay, respectively. The relevance between miR-637 and transient receptor potential melastatin 2 (TRPM2) was checked using TargetScan and dual luciferase reporter gene assay. The expression of miR-637 and TRPM2 was evaluated using qRT-PCR and/or Western blot analysis. Reactive oxygen species (ROS) accumulation, superoxide dismutase (SOD) and catalase (CAT) activities were measured using specific assay kits. In addition, the expression of Bcl-2 and Bax were evaluated using Western blot assay. Results: TRPM2 was up-regulated, while miR-637 was down-regulated in H2O2-stimulated human primary melanocytes. TRPM2 directly interacted with miR-637. Up-regulation of miR-637 memorably increased miR-637 level and inhibited TRPM2 expression. Furthermore, miR-637 mimic fortified cell viability, reduced apoptotic cells, enhanced Bcl-2 expression, reduced Bax level, as well as inhibited the ratio of Bax/Bcl-2 in H2O2-induced melanocytes. Meanwhile, miR-637 mimic obviously suppressed the accumulation of ROS and increased SOD and CAT activity. Nevertheless, all these findings were inverted by TRPM2-plasmid. Likewise, TRPM2-siRNA led to increased cell viability, reduced apoptotic cells, enhanced Bcl-2 expression, reduced Bax level, inhibited Bax/Bcl-2 ratio, inhibited ROS production, but increased SOD and CAT activity in H2O2-induced melanocytes. Conclusion: Our findings suggested that TRPM2 was up-regulated, while miR-637 was down-regulated in injurious melanocytes of vitiligo. Up-regulation of miR-637 relieved oxidative stress-stimulated melanocyte injury via down-regulating TRPM2 expression. Our results provide new insights into the functions of miR-637 in the development of vitiligo, indicating that miR-637 may be a latent target for vitiligo therapy.

Unusual Timeline of Nivolumab-induced Vitiligo in a Patient with Melanoma

Vitiligo, manifested by skin hypopigmentation, is an autoimmune disorder of the skin due to the autoimmune destruction of melanocytes. Nivolumab, which is a programmed cell death–1 receptor inhibitor, is a well-known therapy for melanoma. Nivolumab-induced vitiligo has been described in literature, explained by destruction of non-cancerous melanocytes. This is considered a favorable response, due to a correlated stronger immune response against tumor cells. The average onset of the vitiligo is reported to be 5.2 months after starting the therapy, with a maximum reported onset being 9 months. We present a 52-year-old male patient whose initial vitiligo presentation occurred a year after starting the therapy and has continued for months after concluding Nivolumab therapy.

CLINICAL AND IMMUNOGYCAL ASPECTS OF PATHOGENESIS AND COMPLEX THERAPY OF VITILIGO

Vitiligo is the most common depigmentation disorder where the selective destruction of functioning melanocytes causes depigmentation of the skin, hair and mucosal surfaces. It affects approximately 0.5% to 1% of the population, with an average age of onset at about 24 years, its prevalence appears to be equal between men and women and there is no difference in the rate of occurrence according to skin type or race. Several etiological factors have been suggested for which the most compelling evidence involves a combination of environmental, genetic and immunological factors interacting to contribute to autoimmune melanocyte destruction. Vitiligo is a common skin disorder characterized by depigmented white patches in the skin due to loss of melanocytes. It remains unclear what causes damage or death to the melanocytes, there are many potential pathophysiological theories involving autoimmune, neural, autocytotoxic, biochemical, oxidative stress, melanocytorrhagy, and decreased melanocyte survival hypotheses. Autoimmune theory is more prominent in generalized vitiligo, which is considered a complex disorder involving combined pathogenic effects of multiple susceptibility genes and unknown environmental factors that lead to autoimmune destruction of melanocytes.

Plant-Derived Compounds as Promising Therapeutics for Vitiligo.

Vitiligo is the most common depigmenting disorder characterized by white patches in the skin. The pathogenetic origin of vitiligo revolves around autoimmune destruction of melanocytes in which, for instance, oxidative stress is responsible for melanocyte molecular, organelle dysfunction and melanocyte specific antigen exposure as well as melanocyte cell death and thus serves as an important contributor for vitiligo progression. In recent years, natural products have shown a wide range of pharmacological bioactivities against many skin diseases, and this review focuses on the effects and mechanisms of natural compounds against vitiligo models. It is showed that some natural compounds such as flavonoids, phenols, glycosides and coumarins have a protective role in melanocytes and thereby arrest the depigmentation, and, additionally, Nrf2/HO-1, MAPK, JAK/STAT, cAMP/PKA, and Wnt/β-catenin signaling pathways were reported to be implicated in these protective effects. This review discusses the great potential of plant derived natural products as anti-vitiligo agents, as well as the future directions to explore.

A Concise Review on the Role of Endoplasmic Reticulum Stress in the Development of Autoimmunity in Vitiligo Pathogenesis.

Vitiligo is characterized by circumscribed depigmented macules in the skin resulting due to the autoimmune destruction of melanocytes from the epidermis. Both humoral as well as cell-mediated autoimmune responses are involved in melanocyte destruction. Several studies including ours have established that oxidative stress is involved in vitiligo onset, while autoimmunity contributes to the disease progression. However, the underlying mechanism involved in programing the onset and progression of the disease remains a conundrum. Based on several direct and indirect evidences, we suggested that endoplasmic reticulum (ER) stress might act as a connecting link between oxidative stress and autoimmunity in vitiligo pathogenesis. Oxidative stress disrupts cellular redox potential that extends to the ER causing the accumulation of misfolded proteins, which activates the unfolded protein response (UPR). The primary aim of UPR is to resolve the stress and restore cellular homeostasis for cell survival. Growing evidences suggest a vital role of UPR in immune regulation. Moreover, defective UPR has been implicated in the development of autoimmunity in several autoimmune disorders. ER stress-activated UPR plays an essential role in the regulation and maintenance of innate as well as adaptive immunity, and a defective UPR may result in systemic/tissue level/organ-specific autoimmunity. This review emphasizes on understanding the role of ER stress-induced UPR in the development of systemic and tissue level autoimmunity in vitiligo pathogenesis and its therapeutics.

Association between vitiligo and hearing loss

Vitiligo is a common depigmenting disorder caused by the autoimmune destruction of melanocytes. Some evidence suggests the involvement of melanocytes in the auditory system in the disease process. However, the relationship between vitiligo and sensorineural hearing loss (SNHL) remains uncertain. We investigated the association between vitiligo and SNHL. In this systematic review and meta-analysis, EMBASE, MEDLINE, PubMed, and the Cochrane database were searched for studies examining the association between SNHL and vitiligo from inception to June 28, 2020. A total of 14 case-control studies with 938 patients with vitiligo were included. The meta-analysis showed a significant association of SNHL with vitiligo (odds ratio [OR] 6.02 [95% confidence interval {CI} 3.41-10.62]). The association remained significant after adjustment of study quality and publication bias, with ORs of 5.30 (95% CI 1.53-18.35), and 3.45 (95% CI 1.75-6.81), respectively. Heterogenous definition and measurement of hearing loss and racial differences are potential sources of bias. The evidence to date supports an association of SNHL with vitiligo. These results suggest audiologic assessment for early recognition and management of hearing loss in patients with vitiligo.

Childhood vitiligo: the effect of narrow-band ultraviolet B phototherapy

Vitiligo is an idiopathic acquired disorder characterized by depigmented macules or patches and affects ∼0.5–2% of the worldwide population, without any predilection in terms of sex or ethnicity. It usually begins in childhood or young adulthood. Many etiologic hypotheses have been postulated for vitiligo, including biochemical, neural, and autoimmune mechanisms. The most compelling of these suggests a combination of genetic and immunologic factors that interact and result in an autoimmune melanocyte destruction. Phototherapy using narrow-band ultraviolet B (NB-UVB) with wave length 311–313 nm is considered the treatment of choice in vitiligo, even in childhood. The choice of NB-UVB phototherapy for the treatment of vitiligo has been reported since 1997. Previous studies showed that NB-UVB is a safe treatment for vitiligo in children. NB-UVB is considered more effective and better tolerated than psoralen plus ultraviolet A and shows more stable results.

Skin pigmentation and its control: From ultraviolet radiation to stem cells.

In the light of substantial discoveries in epithelial and hair pigmentation pathophysiology, this review summarizes the current understanding of skin pigmentation mechanisms. Melanocytes are pigment-producing cells, and their key regulating transcription factor is the melanocyte-specific microphthalmia-associated transcription factor (m-MITF). Ultraviolet (UV) radiation is a unique modulator of skin pigmentation influencing tanning pathways. The delayed tanning pathway occurs as UVB produces keratinocyte DNA damage, causing p53-mediated expression of the pro-opiomelanocortin (POMC) gene that is processed to release α-melanocyte-stimulating hormone (α-MSH). α-MSH stimulates the melanocortin 1 receptor (MC1R) on melanocytes, leading to m-MITF expression and melanogenesis. POMC cleavage also releases β-endorphin, which creates a neuroendocrine pathway that promotes UV-seeking behaviours. Mutations along the tanning pathway can affect pigmentation and increase the risk of skin malignancies. MC1R variants have received considerable attention, yet the allele is highly polymorphic with varied phenotypes. Vitiligo presents with depigmented skin lesions due to autoimmune destruction of melanocytes. UVB phototherapy stimulates melanocyte stem cells in the hair bulge to undergo differentiation and upwards migration resulting in perifollicular repigmentation of vitiliginous lesions, which is under sophisticated signalling control. Melanocyte stem cells, normally quiescent, undergo cyclic activation/differentiation and downward migration with the hair cycle, providing pigment to hair follicles. Physiological hair greying results from progressive loss of melanocyte stem cells and can be accelerated by acute stress-induced, sympathetic driven hyperproliferation of the melanocyte stem cells. Ultimately, by reviewing the pathways governing epithelial and follicular pigmentation, numerous areas of future research and potential points of intervention are highlighted.

Elevated serum level of interleukin-15 in vitiligo patients and its correlation with disease severity but not activity.

Vitiligo is a common acquired disorder of depigmentation. Its pathogenesis entails a T helper (Th) 1-cytotoxic T (cT) lymphocytes mediated autoimmune melanocyte destruction. Interleukin (IL)-15 is one of the IL-2 family of cytokines and shares several actions with IL-2. IL-15 enhances survival, maturation, and functional activity of natural killer, neutrophils, and dendritic cells. Furthermore, it potentiates survival, maturation, and cytotoxicity of memory cT cells. IL-15 has been shown to play a crucial role in the pathogenesis of several autoimmune diseases but was poorly investigated in patients with vitiligo. The study aimed at evaluating IL-15 level in the sera of patients with vitiligo and its association with vitiligo severity and activity. The study included 30 patients with nonsegmental vitiligo and 30 healthy controls. Vitiligo Extent Score (VES) and Vitiligo Disease Activity (VIDA) score were used to assess vitiligo severity and activity, respectively. Serum level of IL-15 was assessed by enzyme-linked immune-sorbent assay. Serum IL-15 level, in patients with vitiligo, was significantly higher in comparison with the control group (P=.001). A significant positive correlation was found between serum IL-15 level and VES score (P=.001), whereas there was no significant correlation between IL-15 level and VIDA score as well as the disease duration. IL-15 level was elevated in the sera of patients with vitiligo. IL-15 may therefore have a significant impact on vitiligo autoimmune pathogenesis, and further identification of its molecular roles may highlight new therapeutic strategies for vitiligo.

Mardivirus Infection and Persistence in Feathers of a Chicken Model Harboring a Local Autoimmune Response

Herpesvirus of turkey (HVT) is commonly used as a vaccine to protect chickens against Marek’s disease. Following vaccination, HVT infects feathers where it can be detected in all chicken lines examined. Unlike the parental Brown line (BL), Smyth line (SL) chickens develop vitiligo, due to autoimmune destruction of melanocytes in feathers. Previous reports showed a strong inflammatory response in Smyth chickens’ feathers at vitiligo onset, that subsided once melanocytes were destroyed, and depigmentation was complete. Here, we questioned whether the local autoimmune response in the Smyth model influences HVT infection and persistence in feathers. For this, one-day-old SL and BL chickens were vaccinated with Newcastle disease (rHVT-ND). Vitiligo was scored and HVT loads in pigmented and non-pigmented growing feathers were quantified regularly over 20 weeks. Chickens of both lines showed moderate HVT loads in feathers. At the onset of active vitiligo, the HVT load was significantly higher in SL compared to BL feathers. However, no difference in HVT loads was noticed between pigmented and non-pigmented feathers from SL chickens. Therefore, surprisingly, the inflammatory response in feathers of SL chickens did not inhibit HVT infection and persistence, but on the contrary, temporarily promoted HVT infection in feathers.

Assessment of the Effect of Vitiligo on Subfoveal Choroidal Thickness Using Spectral-Domain Optical Coherence Tomography.

BackgroundVitiligo is a common skin condition affecting 0.5–2% of the population. The exact etiology of the condition is unknown, but the result is autoimmune destruction of melanocytes. The eye is rich in melanocytes, especially in the retinal pigment epithelium and choroid. Little is known about the effect of vitiligo on the choroid of the eye.MethodsWe cross-sectionally examined 31 right eyes of 31 vitiligo patients and 32 right eyes of 32 age- and sex-matched controls for signs of vitiligo affection and then measured the subfoveal choroidal thickness (SFCT) using spectral-domain optical coherence tomography.ResultsThere was a statistically significant difference between SFCT in the cases group and the control group (Mean ± SD: 251.9 ± 42.0 μm and 296.8 ± 46.4 μm, respectively, p = 0.0002). The thickness correlated negatively with age (r = −0.5) but did not correlate significantly with disease severity or duration (r = −0.201, −0.1781, p = 0.2783, 0.3381, respectively). Additional examination findings included iris and fundus hypopigmented spots, and peripapillary atrophy.ConclusionSFCT is reduced among patients with vitiligo. The clinical implications of such a finding should be studied further, and eye screening programs should be considered.

Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway.

Vitiligo is a chronic, autoimmune destruction of melanocytes, resulting in progressively expanding depigmented skin patches. Severity of the disorder, which affects approximately 1% of humans, may be mitigated using topical corticosteroids combined with phototherapy; along with other clinical strategies; however, no definitive cures are currently available. Here, the capacity of apigenin, a plant-derived aglycone, to inhibit oxidative stress-mediated melanocyte depletion in vitro using a PIG3V vitiligo perilesional melanocyte cell model is evaluated. PIG3V cells, treated with selected doses of apigenin, were challenged with H2O2, then assessed for viability and the oxidative stress-related parameters: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) by enzyme-linked immunoabsorbent assay (ELISA). Additionally, expression of nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) and downstream targets was detected using Western blotting. Outcomes demonstrated that compared with negative control cultures, apigenin-treated cells exhibited enhanced viability. Likewise, apigenin enhanced expression of the cellular anti-oxidants SOD, CAT, and GSH-Px, but inhibited production of MDA, an oxidative stress biomarker. Interestingly, the expression and nuclear localization of the Nrf2 transcription factor, an important regulator oxidative stress and its downstream target genes, was significantly increased by apigenin treatment. Apigenin influence on Nrf2 was further validated by experiments demonstrating that Nrf2 knockdown cells failed to exhibit significant apigenin-mediated effects on cell viability and oxidative stress. Apigenin's non-toxicity and ability to affect multiple oxidative stress-related parameters through its effects on Nrf2 signaling in melanocytes suggests that it may prove to be a valuable therapeutic tool in long-term management of vitiligo.

Does psychological stress trigger or exacerbate vitiligo: More data are needed

Background: Vitiligo is a common disorder characterized by depigmentation due to autoimmune destruction of melanocytes. The role of psychological stress in causing vitiligo is not well characterized. Purpose: This article aims at reviewing the role of stress in triggering and/or exacerbating vitiligo. Methods: Seven relevant studies were found in the literature search. Results: Most of the studies support the theory that stressful life events may trigger the onset or the progression of vitiligo. Conclusion: Studies depended mainly on retrospective reporting of stressful events could be a major source of bias.