Autoimmune Etiology of Generalized Vitiligo

Abstract

Vitiligo is characterized by progressive skin depigmentation resulting from an autoimmune response targeting epidermal melanocytes. Melanocytes are particularly immunogenic by virtue of the contents of their melanosomes, generating the complex radical scavenging molecule melanin in a process that involves melanogenic enzymes and structural components, including tyrosinase, MART-1, gp100, TRP-2 and TRP-1. These molecules are also prime targets of the immune response in both vitiligo and melanoma. The immunogenicity of melanosomal proteins can partly be explained by the dual role of melanosomes, involved both in melanin synthesis and processing of exogenous antigens. Melanocytes are capable of presenting antigens in the context of MHC class II, providing HLA-DR+ melanocytes in perilesional vitiligo skin the option of presenting melanosomal antigens in response to trauma and local inflammation. Type I cytokine-mediated immunity to melanocytes in vitiligo involves T cells reactive with melanosomal antigens, similar to T cells observed in melanoma. In vitiligo, however, T cell tuning allows T cells with higher affinity for melanocyte differentiation antigens to enter the circulation after escaping clonal deletion in primary lymphoid organs. The resulting efficacious and progressive autoimmune response to melanocytes provides a roadmap for melanoma therapy.

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…The exact aetiology and detailed pathogenesis of vitiligo is not fully understood, but autoimmunity has been strongly implicated in the development of the disease [5]. The current -of-thehe convergence theory which suggests that several factors can act synergistically or independently to induce the disappearance of melanocytes from the skin [5].…”

“…The current -of-thehe convergence theory which suggests that several factors can act synergistically or independently to induce the disappearance of melanocytes from the skin [5]. In the elicitation phase of vitiligo, triggers including physical trauma to the skin, emotional stresses, and imbalances of endogenous neural factors, metabolites or hormones lead to oxidative stress within melanocytes which then respond by actively secreting heat-shock protein 70 and chaperoned melanocyte antigens [6].…”

New Insights in Mixed Vitiligo: Initial Non Segmental Vitiligo can precede the Onset of Segmental Vitiligo (Cases Report and Review of Theories)

“…According to the "melanocytorrhagy hypothesis", melanocytes of genetically susceptible individuals might be subjected to detachment and consequent cell death following mechanical traumas due to a defect of E-cadherin recently objectivated [13][14][15][16]. Among the numerous environmental factors implicated in the melanocyte loss, immune process has certainly a key role in the pathogenesis of NSV through cell-mediated immunity and also humoral immunity [17][18][19][20]. Moreover, the frequent association of NSV with autoimmune disease could lead to consider it as a systemic disease [21].…”

AFFITOME® technology in neurodegenerative diseases: The doubling advantage

“…This is not only demonstrated by the AN1792 example and the paraneoplastic/autoimmune CNS syndromes but also by the experience with human cancer vaccines. 15 Other potential side effects include, but are not limited to, toxicities associated with specific vaccine components used.…”