Editing Vitiligo (section)

=== Oxidative stress ===
Numerous whole-exome sequencing studies have demonstrated that vitiligo is associated with polymorphisms in genes involved in the response to oxidative stress such as CAT, SOD1, SOD2, SOD3, NFE2L2, HMOX1, GST-M1 or GST-T1 supporting the association of elevated levels of reactive oxygen species in melanocytes with the induction of an auto-immune response.<ref>{{Cite journal | vauthors = Chiarella P |date=2019-10-22 |title=Vitiligo susceptibility at workplace and in daily life: the contribution of oxidative stress gene polymorphisms |journal=Biomedical Dermatology |volume=3 |issue=1 |pages=5 |doi=10.1186/s41702-019-0043-1 |doi-access=free |issn=2398-8460}}</ref><ref>{{cite journal | vauthors = Ezzedine K, Eleftheriadou V, Whitton M, van Geel N | title = Vitiligo | journal = Lancet | volume = 386 | issue = 9988 | pages = 74–84 | date = July 2015 | pmid = 25596811 | doi = 10.1016/S0140-6736(14)60763-7 }}</ref>

Thus, diseases presenting with altered mitochondrial function such as MELAS, Vogt-Koyanagi-Harada syndrome and Kabuki syndrome are associated with increased risk of vitiligo.<ref>{{cite journal | vauthors = Karvonen SL, Haapasaari KM, Kallioinen M, Oikarinen A, Hassinen IE, Majamaa K | title = Increased prevalence of vitiligo, but no evidence of premature ageing, in the skin of patients with bp 3243 mutation in mitochondrial DNA in the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) | journal = The British Journal of Dermatology | volume = 140 | issue = 4 | pages = 634–639 | date = April 1999 | pmid = 10233312 | doi = 10.1046/j.1365-2133.1999.02761.x | first6 = And }}</ref><ref>{{cite journal | vauthors = Liang L, Tan X, Zhou Q, Tian Y, Kijlstra A, Yang P | title = TLR3 and TLR4 But not TLR2 are Involved in Vogt-Koyanagi- Harada Disease by Triggering Proinflammatory Cytokines Production Through Promoting the Production of Mitochondrial Reactive Oxygen Species | journal = Current Molecular Medicine | volume = 15 | issue = 6 | pages = 529–542 | date = 2015-08-19 | pmid = 26238371 | doi = 10.2174/1566524015666150731095611 }}</ref><ref>{{cite journal | vauthors = Margot H, Boursier G, Duflos C, Sanchez E, Amiel J, Andrau JC, Arpin S, Brischoux-Boucher E, Boute O, Burglen L, Caille C, Capri Y, Collignon P, Conrad S, Cormier-Daire V, Delplancq G, Dieterich K, Dollfus H, Fradin M, Faivre L, Fernandes H, Francannet C, Gatinois V, Gerard M, Goldenberg A, Ghoumid J, Grotto S, Guerrot AM, Guichet A, Isidor B, Jacquemont ML, Julia S, Khau Van Kien P, Legendre M, Le Quan Sang KH, Leheup B, Lyonnet S, Magry V, Manouvrier S, Martin D, Morel G, Munnich A, Naudion S, Odent S, Perrin L, Petit F, Philip N, Rio M, Robbe J, Rossi M, Sarrazin E, Toutain A, Van Gils J, Vera G, Verloes A, Weber S, Whalen S, Sanlaville D, Lacombe D, Aladjidi N, Geneviève D | title = Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals | journal = Genetics in Medicine | volume = 22 | issue = 1 | pages = 181–188 | date = January 2020 | pmid = 31363182 | doi = 10.1038/s41436-019-0623-x }}</ref>

In line with these observations, genetic alterations in mitochondrial DNA (mtDNA) of melanocytes associated with altered mitochondrial function lead to a release of mtDNA that can be detected in the skin of vitiligo patients.<ref name=":1">{{cite journal | vauthors = Sant'Anna-Silva AC, Botton T, Rossi A, Dobner J, Bzioueche H, Thach N, Blot L, Pagnotta S, Kleszczynski K, Steinbrink K, Mazure NM, Rocchi S, Krutmann J, Passeron T, Tulic MK | title = Vitiligo auto-immune response upon oxidative stress-related mitochondrial DNA release opens up new therapeutic strategies | journal = Clinical and Translational Medicine | volume = 14 | issue = 8 | pages = e1810 | date = August 2024 | pmid = 39113238 | pmc = 11306283 | doi = 10.1002/ctm2.1810 }}</ref><ref>{{cite journal | vauthors = Bzioueche H, Simonyté Sjödin K, West CE, Khemis A, Rocchi S, Passeron T, Tulic MK | title = Analysis of Matched Skin and Gut Microbiome of Patients with Vitiligo Reveals Deep Skin Dysbiosis: Link with Mitochondrial and Immune Changes | journal = The Journal of Investigative Dermatology | volume = 141 | issue = 9 | pages = 2280–2290 | date = September 2021 | pmid = 33771527 | doi = 10.1016/j.jid.2021.01.036 }}</ref> This mtDNA can be sensed by the cGAS-STING pathway resulting in pro-inflammatory cytokine and chemokines production promoting the recruitment of cytotoxic CD8+ T cells. The use of mitochondrial antioxidants, NRF2 inhibitors, and TBK1 inhibitors is emerging as potential therapeutic options to block this cascade of events.<ref name=":1" />