Autoimmune Aspects of Depigmentation in Vitiligo

Abstract

Autoimmune depigmentation of the skin, vitiligo, afflicts a considerable number of people, yet no effective therapeutic modalities have been developed to treat it. In part, this can be attributed to the obscure etiology of the disease, which has begun to reveal itself only recently. It is known that pigment is lost as a function of reduced melanocyte numbers in the epidermis, and that depigmentation is accompanied by T cell influx to the skin in the vast majority of patients. Characterizing such infiltrating T cells as type 1 proinflammatory cytokine-secreting cells reactive with melanocyte-specific antigen is a major step toward effective therapy. Melanoma research has shown that differentiation antigens, also expressed by normal melanocytes, can be immunogenic when expressed in the melanosomal compartment of the cell. Similar reactivity to melanosomal antigens is apparent for T cells infiltrating vitiligo skin. It may eventually be possible to treat patients with decoy antigens that anergize such Tcells, or to prevent recruitment of the T cells to the skin altogether. In this respect, it is important that T cells are recruited to the skin as a function of dendritic cell activation and that dendritic cells are likely activated at sites of epidermal trauma as a consequence of stress proteins that spill over into the microenvironment. Stress proteins chaperoning antigens representative of the cells from which they were derived are then processed by dendritic cells and contribute to their activation. Activated dendritic cells not only migrate to draining lymph nodes to recruit T cells but may execute cytotoxic effector functions as well. The contribution of the effector functions to actual depigmentation of the skin remains to be investigated.

Shared Genetic Relationships Underlying Generalized Vitiligo and Autoimmune Thyroid Disease

“…Melanocyte loss in generalized vitiligo occurs primarily on an autoimmune basis (7,(30)(31)(32), although the triggers of the autoimmune response remain unknown. Many patients have circulating antibodies to various melanocyte components, most frequently tyrosinase (33), the key enzyme of melanin biosynthesis (34), as well as circulating skin-homing melanocytespecific cytotoxic T-lymphocytes (35).…”

Beta Adrenergic Receptors in Keratinocytes

“…Many theories have been proposed for the pathogenesis of vitiligo, including genetic, autoimmune, and oxidative damage etiologies (reviewed in [13,51,52]). One pathogenic mechanism advanced by the work of Schallreuter and colleagues implicates the beta2AR signaling pathway and catecholamine synthetic network within the epidermis (recently reviewed in [13]).…”

A case-control study: evaluation of vitamin D metabolism in patients with vitiligo

“…Its immunopathogenesis is not completely understood but autoimmune etiology appears to be the most plausible (1). The relationship of vitiligo with other autoimmune disorders, and especially its coexistence with autoimmune thyroid diseases, has previously been reported (2,3). Recently, many autoimmune diseases including vitiligo have been found to be associated with reduced vitamin D levels (4,5).…”