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Vitiligo and gene therapy

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https://www.readbyqxmd.com/read/27635239/recent-advances-in-understanding-vitiligo
#1
REVIEW
Prashiela Manga, Nada Elbuluk, Seth J Orlow
Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation...
2016: F1000Research
https://www.readbyqxmd.com/read/27314920/vitiligo-therapy-restoring-immune-privilege
#2
Katia Boniface, Julien Seneschal, Alain Taïeb, Aksam Merched
The therapeutic hypothesis proposed by Speeckaert and van Geel in this issue (1) is based on the dramatic effect of the new drugs targeting immune privilege checkpoints (PD1/PD-L1, CTLA4) in current advanced melanoma therapy as major inducers of vitiligo-like skin changes. Such striking clinical manifestations cannot be classified as mere adverse effects without considering possible consequences for spontaneously occurring vitiligo. GWAS revealed more than 35 loci significantly associated with vitiligo (2)...
June 17, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27221340/pigment-production-analysis-in-human-melanoma-cells
#3
Amelia Soto Hopkin, Elyse K Paterson, Rolando Ruiz, Anand K Ganesan
The human epidermal melanocyte is a highly specialized pigmented cell that serves to protect the epidermis from ultraviolet (UV) damage through the production of melanin, or melanogenesis. Misregulation in melanogenesis leading to either hyper- or hypo-pigmentation is found in human diseases such as malasma and vitiligo. Current therapies for these diseases are largely unsuccessful and the need for new therapies is necessary. In order to identify genes and or compounds that can alter melanogenesis, methods are required that can detect changes in pigment production as well as expression of key melanogenesis transcription factors and enzymes...
May 25, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26957557/cytotoxic-cutaneous-adverse-drug-reactions-during-anti-pd-1-therapy
#4
Simone M Goldinger, Pascale Stieger, Barbara Meier, Sara Micaletto, Emmanuel Contassot, Lars E French, Reinhard Dummer
PURPOSE: Immunotherapy has experienced impressive progress in cancer treatment. Antibodies against PD-1 improved survival in different types of cancer including melanoma. They are generally well tolerated. However, skin toxicities including pruritus, rashes, and vitiligo are reported. Although frequent, they have not been characterized further yet. In this analysis, we aimed to systematically assess and characterize the adverse cutaneous reactions observed in patients with melanoma treated with anti-PD-1 antibodies...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26387449/vitiligo-how-do-oxidative-stress-induced-autoantigens-trigger-autoimmunity
#5
REVIEW
Heng Xie, Fubo Zhou, Ling Liu, Guannan Zhu, Qiang Li, Chunying Li, Tianwen Gao
Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes...
January 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/26315342/oxidative-stress-induced-overexpression-of-mir-25-the-mechanism-underlying-the-degeneration-of-melanocytes-in-vitiligo
#6
Q Shi, W Zhang, S Guo, Z Jian, S Li, K Li, R Ge, W Dai, G Wang, T Gao, C Li
Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo...
March 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/25965418/a-functional-single-nucleotide-polymorphism-in-the-ercc1-gene-alters-the-efficacy-of-narrowband-ultraviolet-b-therapy-in-patients-with-active-vitiligo-in-a-chinese-population
#7
W Dai, F-B Zhou, C Wei, X-W Wang, S Guo, X-L Yi, K Li, T-W Gao, L Liu, C-Y Li
BACKGROUND: T lymphocytes have been shown to cause the destruction of melanocytes in vitiligo pathogenesis. Narrowband ultraviolet B (NB-UVB), as an effective therapeutic strategy in vitiligo, can lead to the formation of DNA photoproducts such as cyclobutane pyrimidine dimers (CPDs) in perilesional lymphocytes and thus induce skin immunosuppression. The repair of DNA photoproducts is performed mainly through the nucleotide excision repair (NER) pathway. We hypothesized that single-nucleotide polymorphisms (SNPs) in NER genes might influence the repair capacity of CPDs and thus contribute to variations in phototherapy efficiency...
August 2015: British Journal of Dermatology
https://www.readbyqxmd.com/read/24494059/a-pilot-study-assessing-the-effect-of-prolonged-administration-of-high-daily-doses-of-vitamin-d-on-the-clinical-course-of-vitiligo-and-psoriasis
#8
Danilo C Finamor, Rita Sinigaglia-Coimbra, Luiz C M Neves, Marcia Gutierrez, Jeferson J Silva, Lucas D Torres, Fernanda Surano, Domingos J Neto, Neil F Novo, Yara Juliano, Antonio C Lopes, Cicero Galli Coimbra
Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described in affected patients. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. This study aimed to assess the efficacy and safety of prolonged high-dose vitamin D3 treatment of patients with psoriasis and vitiligo. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya "milk") and hydration (minimum 2...
January 1, 2013: Dermato-endocrinology
https://www.readbyqxmd.com/read/24300644/biology-and-genetics-of-oculocutaneous-albinism-and-vitiligo-common-pigmentation-disorders-in-southern-africa
#9
Prashiela Manga, Robyn Kerr, Michèle Ramsay, Jennifer G R Kromberg
Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively)...
December 2013: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/24019775/diphenylcyclopropenone-induced-vitiligo-in-a-patient-with-alopecia-universalis
#10
Hassan Riad, Haya Al Mannai, Khalid Mansour, Khalifa Al Qaatri, Sharifa Al Dosari, Amina Al Obaidaly, Emad Sultan
Alopecia areata and vitiligo are autoimmune diseases, both associated with multiple autoimmune comorbidities. Many studies show colocalization of these diseases at the same anatomical site. Here, we have a case where both disorders were reported to present in the same patient. Diphenylcyclopropenone (diphencyprone, DCP) is used in the treatment of alopecia areata and may induce vitiligo in some patients. We report on one case of vitiligo that was induced by DCP during therapy for alopecia universalis. Alopecia areata and vitiligo share many susceptibility genes...
2013: Case Reports in Dermatology
https://www.readbyqxmd.com/read/23782102/stimulated-human-melanocytes-express-and-release-interleukin-8-which-is-inhibited-by-luteolin-relevance-to-early-vitiligo
#11
A Miniati, Z Weng, B Zhang, A Therianou, M Vasiadi, E Nicolaidou, A J Stratigos, C Antoniou, T C Theoharides
Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)-8 (CXCL8) is a key inflammatory chemokine. We investigated the regulation of IL-8 production in human melanocytes, and the IL-8 serum levels and skin gene expression in patients with vitiligo and in controls. Cultured melanocytes were stimulated for 24 h with tumour necrosis factor (TNF) 100 ng/mL and IL-1β 10 ng/mL, with or without pretreatment with luteolin 50 μmol/L for 30 min, and IL-8 release was measured by ELISA...
January 2014: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/23398671/irradiance-but-not-fluence-plays-a-crucial-role-in-uvb-induced-immature-pigment-cell-development-new-insights-for-efficient-uvb-phototherapy
#12
Cheng-Che E Lan, Hsin-Su Yu, Jian-He Lu, Ching-Shuang Wu, Hsiao-Chi Lai
Light exposure modulates development of living organisms. In the field of medicine, light has frequently been used for regenerative purposes. Excimer light (308 nm) has demonstrated superior efficacy in treating vitiligo, a condition requiring development of melanoblasts and a model for studying nerve cell regeneration, as compared to narrow-band ultraviolet B (NBUVB; 311 nm). Using mouse-derived melanoblast cells to examine the pro-differentiation effects of these two light sources, we demonstrated that at equivalent fluence, excimer light induces melanoblast differentiation, while NBUVB failed to so...
May 2013: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/23251420/transcriptome-analysis-reveals-markers-of-aberrantly-activated-innate-immunity-in-vitiligo-lesional-and-non-lesional-skin
#13
Richard Yu, Raewyn Broady, Yuanshen Huang, Yang Wang, Jie Yu, Min Gao, Megan Levings, Shencai Wei, Shengquan Zhang, Aie Xu, Mingwan Su, Jan Dutz, Xuejun Zhang, Youwen Zhou
BACKGROUND: Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients...
2012: PloS One
https://www.readbyqxmd.com/read/23182677/polyglandular-autoimmune-syndrome-type-i
#14
REVIEW
Emmanuelle Proust-Lemoine, Pascale Saugier-Veber, Jean-Louis Wémeau
Polyglandular Autoimmune Syndrom type 1 (PAS-1) or Autoimmune PolyEndocrinopathy Candidiasis-Ectodermal-Dystrophy (APECED) is a rare recessive autosomal disease related to Autoimmune Regulator (AIRE) gene mutations. AIRE is mainly implicated in central and peripheric immune tolerance. Diagnosis was classically based on presence of at least two out of three "majors" criterions of Whitaker's triad (candidiasis, autoimmune hypoparathyroidism and adrenal insufficiency). Presence of one criterion was sufficient when a sibling was previously diagnosed...
December 2012: La Presse Médicale
https://www.readbyqxmd.com/read/22999738/intelligent-bioengineering-in-vitiligo-treatment-transdermal-protein-transduction-of-melanocyte-lineage-specific-genes
#15
Yi Mou, Xian Jiang, Yu Du, Li Xue
Vitiligo is a common, incurable skin disease with a prevalence of about 1%. Although many vitiligo therapies are available in clinics, there is almost no one method that causes significant improvement in all vitiligo patients. Some have hypothesized that melanocyte dysfunction or deficiency underlies the loss of skin pigmentation observed in vitiligo. The autoimmune-mediated apoptosis of melanocytes might be an important part of the etiology of vitiligo, which prevents the formation of melanocytes in the skin...
December 2012: Medical Hypotheses
https://www.readbyqxmd.com/read/22958397/potent-melanin-production-enhancement-of-human-tyrosinase-gene-by-tat-and-an-entrapment-in-elastic-cationic-niosomes-potential-application-in-vitiligo-gene-therapy
#16
Jiradej Manosroi, Narinthorn Khositsuntiwong, Friedrich Götz, Rolf G Werner, Worapaka Manosroi, Aranya Manosroi
Potent melanin production enhancement of human tyrosinase plasmid (pAH7/Tyr, P) in mouse melanoma cells (B(16)F(10)) by Tat peptide (T) and an entrapment in elastic cationic niosomes (E) was described. The E composed of Tween 61/cholesterol/dodecyl dimethyl ammonium bromide at 1:1:0.5 molar ratio was prepared by freeze-dried emptying liposomes method. PE at P/E ratio of 1:160 w/w and TPE at T/P/E ratio of 0.125:1:160, 0.25:1:160, and 0.5:1:160 w/w/w were prepared. The final concentration of the plasmid in the study was 4 ng/μL...
December 2012: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/22943168/enhancement-of-gene-expression-and-melanin-production-of-human-tyrosinase-gene-loaded-in-elastic-cationic-niosomes
#17
Narinthorn Khositsuntiwong, Aranya Manosroi, Friedrich Götz, Rolf G Werner, Worapaka Manosroi, Jiradej Manosroi
OBJECTIVES: Disturbance in the synthesis of tyrosinase might be one of the major causes of vitiligo. The enhancement of tyrosinase gene expression and melanin production by loading the plasmid in elastic cationic niosomes was investigated in tyrosinase gene knocked out human melanoma (M5) cells and in tyrosine-producing mouse melanoma (B(16) F(10) ) cells. METHODS: Niosomes composed of Tween 61/cholesterol/dimethyl dioctadecyl ammonium bromide at 1:1:0.5 molar ratio were prepared by the freeze-dried empty liposomes method...
October 2012: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/22569306/baicalein-protects-human-melanocytes-from-h%C3%A2-o%C3%A2-induced-apoptosis-via-inhibiting-mitochondria-dependent-caspase-activation-and-the-p38-mapk-pathway
#18
Bangmin Liu, Zhe Jian, Qiang Li, Kai Li, Zhiyong Wang, Ling Liu, Lingzhen Tang, Xiuli Yi, Hua Wang, Chunying Li, Tianwen Gao
The removal of H(2)O(2) by antioxidants has been proven to be beneficial to patients with vitiligo. Baicalein (5,6,7-trihydroxyflavone; BE) has antioxidant activity and has been used in vitiligo therapy in Chinese traditional medicine. In this study, we investigated the potential protective effect and mechanisms of BE against H(2)O(2)-induced apoptosis in human melanocytes. Melanocytes from the PIG1 cell line were pretreated with different concentrations of BE for 1 h, followed by exposure to 1.0 mM H(2)O(2) for 24 h...
July 15, 2012: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/22391242/the-effects-of-nb-uvb-on-the-hair-follicle-derived-neural-crest-stem-cells-differentiating-into-melanocyte-lineage-in-vitro
#19
Dake Dong, Min Jiang, Xiaowei Xu, Ming Guan, Jiaqiang Wu, Qinyi Chen, Leihong Xiang
BACKGROUND: Narrow-band UVB (NB-UVB) is an effective therapeutic option in the treatment of vitiligo. Despite the apparent clinical efficacy, the underlying mechanism of how topical NB-UVB induces repigmentation in vitiligo has not been clearly elucidated. OBJECTIVES: To investigate the effects of NB-UVB on the maturation of melanocyte lineage differentiated from hair follicle-derived neural crest stem cells (HF-NCSCs) in vitro. METHODS: HF-NCSCs were isolated from mouse whisker follicles...
April 2012: Journal of Dermatological Science
https://www.readbyqxmd.com/read/22151832/basic-fibroblast-growth-factor-and-tumour-necrosis-factor-alpha-in-vitiligo-and-other-hypopigmented-disorders-suggestive-possible-therapeutic-targets
#20
COMPARATIVE STUDY
H Seif El Nasr, O G Shaker, M M T Fawzi, G El-Hanafi
BACKGROUND: In healthy skin, there is a molecular microenvironment that favours the survival of melanocytes and regulates their function. Keratinocytes synthesize and secrete several cytokines that have stimulatory and inhibitory effects on melanocytes. AIM OF THE WORK: This work was conducted to evaluate the expression of basic fibroblast growth factor (bFGF) and tumour necrosis factor alpha (TNF-α) mRNA levels in lesional skin of vitiligo, hypopigmented mycosis fungoides and hypopigmented tinea versicolor...
January 2013: Journal of the European Academy of Dermatology and Venereology: JEADV
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