DOI: 10.5281/zenodo.6997416
title: MELAN-A EXPRESSION RELATED TO APOPTOSIS OF MELANOCYTES IN SEGMENTAL AND NONSEGMENTAL VITILIGO

description: <strong>Abstract</strong> <strong>Background: </strong>Vitiligo is a progressive depigmentation of the skin with unclear etiology. Cell-mediated immunity has been suggested to play an important role in the pathogenesis of vitiligo’s progression. Melan-A has a high affinity for specific CD8+ T cells and is one of the critical markers for detecting damage to melanocytes. <strong>Aim: </strong>Our study aims to demonstrate the differences of Melan-A expression associated with apoptosis of melanocytes in patients with segmental vitiligo (SV) and those with non-segmental vitiligo (NSV). <strong>Methods:</strong> The subjects consisted of 64 patients diagnosed with vitiligo, of whom 33 were with NSV and 31 with SV. Skin biopsy and direct immunofluorescence were used to examine Melan-A, and the TUNEL method was performed to examine melanocyte apoptosis in both groups. Group comparisons were conducted using appropriate statistical methods. <strong>Results: </strong>Melan-A expression was significantly higher in the NSV group than in the SV group, and there was a significant difference between two groups (p = 0.001). The median of melanocyte apoptosis in the NSV group was relatively higher than in the SV group, and a significant difference was found between the two groups (p = 0.001). The Spearman’s rank correlation test between Melan-A expression and melanocyte apoptosis in the NSV group was 0.767 (76.7%) and showed a significant relationship (p &lt;0.05). The same test in the SV group was 0.583 (58.3%) and showed a significant relationship (p &lt;0.05). In both groups, the higher the Melan-A expression, the higher the melanocyte apoptosis. <strong>Conclusion:</strong> Melan-A expression and melanocyte apoptosis are correlated. The higher Melan-A expression and melanocyte apoptosis in NSV indicates more severe vitiligo disease compared to SV.
description: {"references": ["1.\tHabib A. Clinical profile of segmental vitiligo in a group of Pakistani patients. Pak Armed Forces Med J. 2019;69(3):495-99.", "2.\tRelke N, Gooderham M. The use of Janus kinase inhibitors in vitiligo: a review of the literature. J Cutan Med Surg. 2019;23(3):298-306.", "3.\tKaragaiah P, Schwartz RA, Lotti T, Wollina U, Grabbe S, Goldust M. Biologic and targeted therapeutics in vitiligo. J Cosmet Dermatol. 2022.", "4.\tKang S, Amagai M, Bruckner A, Enk A, Margolis D, McMichael A, Orringer J. Fitzpatrick's dermatology. 9th ed. New York: McGraw-Hill; 2019.", "5.\tDelmas V, Larue L. Melanocyte homeostasis in vitiligo. Vitiligo. 2019;265-275. doi:10.1007/978-3-319-62960-5_26", "6.\tAbdel\u2010Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I. The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res. 2020;33(6):778-787.", "7.\tPicardo M. (2019). Pathophysiology overrview. Vitiligo. 189-192. doi: 10.1007/978-3-319-62960-5_20", "8.\tHarris JE. What causes vitiligo? Vitiligo Clinic and Research. 1-2.", "9.\tBoniface K, Seneschal J, Picardo M, Taieb A. Vitiligo: focus on clinical aspects, immunopathogenesis, and therapy. Clin Rev Allergy ImmunolZ 2018;54(1):52-67. doi: 10.1007/s12016-017-8622-7.", "10.\tHann S, Yu HS, Lan C-CE, Wu CS, Gauthier Y, Benzekri L, Taieb A. Segmental vitiligo. Vitiligo. 2019;53-71.doi: 10.1007/978-3-319-62960-5_6.", "11.\tXie H, Zhou F, Liu L, Zhu G, Li Q, Li C, Gao T. Vitiligo: how do oxidative strss-induced autoantigens triger autoimmunity? J Dermatol Sci. 2016;81(1):3-9. doi:10.1016/j.jdermsci.2015.09.00", "12.\tArora A, Kumaran M. Pathogenesis of vitiligo: an update. Pigment Int. 2017;4(2):65. doi: 10.4103/2349-5847.219673", "13.\tKubanov A, Proshutinskala VV, Katunina O, Abrarmova T. Immununohistochemichal analysis of melanocyte content in different zones of vitiligo lesions using the Melan-A marker. Acta Derm. 2015;25:5-9. doi:10.15570/actaapa.2016.2", "14.\tCosta C, Kovacs D. Vitiligo: histopathology, including electron microscopy. Vitiligo. 2019;25-37. doi: 10.1007/978-3-319-62960-5_3", "15.\tBabai S, Voisin AL, Bertin C, Gouverneur A, Le Louet H Occurrences and outcomes of immune checkpoint inhibitors-induced vitiligo in cancer patients: a retrospective cohort study. Drug Safety. 2019. doi:10.1007/s40264-019-00875-6", "16.\tAwad SS, Tadros E. Understanding the role of lymphocytes in vitiligo. Int J Immunol Immunother. 2021;7:60. doi:10.23937/2378-3672/1410060", "17.\tPraharsini IGAA, Suryawati N, Indira IE, Sanjiwani SP. (2018). High level of tumor necrosis alpha and serum interferon gamma as risk factors for progression of vitiligo disease. Int J Health Sci. 2018;2(2):1-8.", "18.\tChen X, Guo W, Chang Y, Chen J, Kang P, Yi X, Cui T, Guo S, Xiao Q, Jian Z, Li C. Oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to CD8+ T cells activation via JAK-STAT pathway in vitiligo. Free Radic Biol Med. 2019;139: 80-91.", "19.\tKundu RV, Mhlaba JM, Rangel SM, Poole IC. The convergence theory for vitiligo: a reappraisal. Exp Dermatol. 2018. doi:10.1111/exd.1367z", "20.\tSpeeckaert R, Van Geel N. Vitiligo: an update on pathophysiology and treatment options, Article Reviews, 2017;18(June):733-744. doi:10.1007/s40257-017-0298_5", "21.\tSpeeckaer R, Speeckaert M, De Schepper S, Van Geel N. Biomarkers of disease activity in vitiligo: a systematic review. Autoimmun Rev. 2017;16(9):937-945. doi:10.1016/j.autrev.2017.07.005", "22.\tNa N, Park J. A new approach using a numerical diagnostic criterion for vitiligo diagnosis with HMB-45 and Melan-A staining. Int J Clin Exp Pathology. 2021;14(8):902-907.", "23.\tZhang L, Chen S, Kang Y, Wang X, Yan F, Jiang M, Wang Q, Liu Z, Zhang C, Xiang L. Association of clinical markers with disease progression in patiens with vitiligo from China. JAMA Dermatol. 2019. doi:10.1001/jamadermatol.2019.4483", "24.\tWebb KC, Henning SW, Le Poole IC. Immunity/Immunopathology. Vitiligo. 2019;285-301. doi:10.1007/978-3-319-62960-5_28", "25.\tBerqvist C, Ezzdine K. Vitiligo: a review. Review Article of Dermatology. 2020;1-22. doi:10.1159/000506103", "26.\tIannella G, Greco A, Didona D, Didona B, Granata G, Manno A, Pasquariello B, Magliulo G. Vitiligo: pathogenesis, clinical variants and treatment approaches. Autoimmun Rev. 2016;15(December):335-343. doi:10.1016/j.autrev.2015.12", "27.\tRuiz-Arg\u00fcelles A, Brito GJ, Reyes-Izquierdo P, P\u00e9rez-Romano B, S\u00e1nchez-Sosa S. Apoptosis of melanocytes in vitiligo results from antibody penetration. J Autoimmun. 2017;29(4):281-286. doi:10.1016/j.jaut.2007.07.012", "28.\tFrisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38(1). doi:10.1146/annurev-immunol-100919-023531", "29.\tSingh M, Kotnis A, Jadeja SD, Mondal A, Mansuri MS, Begum R. Cytokines: the yin and yang of vitiligo pathogenesis. Expert Rev Clin Immunol. 2018. doi:10.1080/1744666x.2019.1550358", "30.\tPark K, Lee SE, Shin K-Oh, Uchida Y. Insights into the role of endoplasmic reticulum stress in skin function and assciated diseases. Review Article. FEBS J. 2019;413-425. doi: 10.1111/febs.1473", "31.\tPatel S, Rauf A, Khan H, Meher BR, Hassan SS. A holistic review on the autoimmune disease vitiligo with emphasis on the causal factors. Biomed Pharmacother. 2017;92:501\u2013508. doi:10.1016/j.biopha.2017.05.095", "32.\tAvalos-D\u00edaz E, P\u00e9rez-P\u00e9rez E, Rodr\u00edguez-Rodr\u00edguez M, Pacheco-Tovar M-G, Herrera-Esparza R. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population. Biomed Rep. 2016;5(2):176-180.", "33.\tRodrigues M, Ezzedine K, Hamzavi I, Pandya G, Harris J. New discoveries in the pathogenesis and classification of vitiligo, J Am Acad Dermatol. 2017;77(July):1-13.", "34.\tScaturro P, Pichlmair A. Oxeiptosis: a discreet way to respond to radicals. Curr Opin Immunol. 2019;56:37\u201343. doi:10.1016/j.coi.2018.10.006", "35.\tAbbas AK, Lichtman AH, Pillai S. (2018). Cellular and mollecular immunology. 9th ed. Winsland: Elsevier.", "36.\tJimbo H, Nagai H, Fujiwara S, Shimoura N, Nishigori C. (2019). Fas-FasL interaction factor and interferon in Fas-mediated melanocyte apoptosis. Exp Dermatol. 2019;61-69. doi10.1111/exd.14053", "37.\tJohnson JD, Barnard DF, Kulp AC, Mehta DM. Neuroendocrine regulation of brain cytokines after psychological stress. J Endocr Soc. 2019;3(7):1302\u20131320. doi:10.1210/js.2019-00053", "38.\tTang L, Li J, Fu W, Wu W, Xu J. Supression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanosit: Implications for votiligo. Research Paper. 2019;11(24). doi.10.18632/aging.102452", "39.\tKiselevsky DB. Granzymes and Mitochondria. Biochemistry (Moscow). 2020;85(2):131\u2013139. doi:10.1134/s0006297920020017", "40.\tVaniary TIN, Listiawan MY, Murtiastutik D. Expression of Melan-A in depigmented skin of vitiligo patients. Berkala Ilmu Kesehatan Kulit dan Kelamin, 2020;32(1):17-20."]}