title: Vitiligo puzzle: the pieces fall in place.
abstract: Over the years, the role of biochemical, immunological, genetic, and other biological aspects in the pathogenesis of vitiligo has been studied. So far, no convincing model describing the interplay of these contributing factors has been formulated. Based on existing research, we propose that vitiligo has a multi-factorial etiology, characterized by multiple steps, but always involving an increase of external or internal phenol/catechol concentration, serving as a preferred surrogate substrate of tyrosinase, competing with its physiological substrate tyrosine. The conversion of these substrates into reactive quinones is reinforced by a disturbed redox balance (increasing hydrogen peroxide). Such reactive quinones can be covalently bound to the catalytic centre of tyrosinase (haptenation). This could give rise to a new antigen, carried by Langerhans cells to the regional lymph node, stimulating the proliferation of cytotoxic T cells. However, the activation of such cytotoxic cells is only a first step in skin melanocyte killing, which also depends on a shift in the balance between immune defence and tolerance, e.g. resulting from a decrease in properly functioning T-regulatory cells. With this new model, based on a synthesis of several of the existing theories, in mind, the external and internal factors involved in the etiopathogenesis of vitiligo are reviewed, against the background of reported clinical data, experimental studies and existing and potential new therapies. A similar complex mechanism may also lead to some other autoimmune diseases.
authors.affiliation: Color Foundation, Landsmeer, The Netherlands. w.westerhof@amc.uva.nl
authors.forename: Wiete
authors.initials: W
authors.lastname: Westerhof
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis; D016227:Benzoquinones / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D008957:Models, Genetic; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009784:Occupational Diseases / Q000175:diagnosis; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species; D013601:T-Lymphocytes / Q000378:metabolism; D014820:Vitiligo / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology*
chemical_list: D016227:Benzoquinones; D017382:Reactive Oxygen Species; C004532:quinone; D014442:Monophenol Monooxygenase