Vitiligo Metabolic/Biochemical Hypothesis
Another hypothesis of melanocyte destruction suggests it may be an end result of metabolic and biochemical dysregu-lation. Keratinocytes and melanocytes may have innate biochemical abnormalities, particularly in the metabolism of biopterins and catechols, which increase susceptibility to reactive oxygen species and immunologic cytotoxicity. The oxidative stress hypothesis is supported by studies that found an imbalance in oxidative-reduction (redox) status in peripheral blood mononuclear cells in vitiligo patients, which represents the redox status of the epidermis. Additionally, elevated levels of hydrogen peroxide [H.sub.2] [O.sub.2] can be found in the epidermis of vitiligo patients along with lower levels of the antioxidant catalase. Some have proposed that vitiligo is a systemic disease of redox imbalance that manifests with cutaneous lesions.
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It is possible that oxidative stress induces an immune reaction that ultimately induces melanocyte death. It has been reported that stress such as overexposure to ultraviolet (UV) light, contact with bleaching phenols, emotional stress, and mechanical injury can precipitate vitiligo. Melanocytes from vitiligo lesions have also been shown to express increased amounts of heat shock protein (HSP) 70 as compared to normal melanocytes. Heat shock proteins are expressed by cells under stress, act as chaperones, and prevent cells from undergoing apoptosis. Heat shock protein 70 in particular is unique in that it is secreted by live cells and, once it is released, enhances the antigen uptake of dendritic cells (DCs), activates the DCs, and ultimately stimulates a T-cell immune response. By chaperoning proteins and peptides out of the cells, and perhaps secreting melanosomes with (HSP) 70, it is postulated that the combination of HSP70 with these antigens induces an immune reaction against melanocytes. A recent study took this concept further by using a mouse model of autoimmune vitiligo induced by gene gun vaccination with melanocyte antigens. They showed that including human and mouse-derived inducible HSP70 in the protocol increased and accelerated depigmentation. HSP70 may link the biochemical/metabolic hypothesis with the autoimmune hypothesis of vitiligo. An increased level of oxidative stress in vitiligo melanocytes may get translated into an immune response.[ad#post-bottom]