Functional cloning of a gp100-reactive T-cell receptor from vitiligo patient skin.

We isolated gp100-reactive T cells from perilesional skin of a patient with progressive vitiligo with superior reactivity toward melanoma cells compared with tumor-infiltrating lymphocytes 1520, a melanoma-derived T-cell line reactive with the same cognate peptide. After dimer enrichment and limited dilution cloning, amplified cells were subjected to reverse transcription and 5' RACE to identify the variable TCRα and TCRβ subunit sequences. The full-length sequence was cloned into a retroviral vector separating both subunits by a P2A slippage sequence and introduced into Jurkat cells and primary T cells.

The effect of H₁ and H₂ receptor antagonists on melanogenesis.

Background: Histamine was found to stimulate melanogenesis in cultured human melanocytes specifically mediated by histamine H 2 receptors via protein kinase A activation. Based on this finding, the effect of topically applied H 2 antagonist on UVB-irradiated Guinea pigs' skin was examined and found to be suppressive on the post-irradiation melanogenesis.

Aims: In this study, we tried to explore the role of topically applied H 1 and H 2 receptor antagonists, in inhibition of UVB-induced melanization.

Koebner's phenomenon in vitiligo: European position paper.

Koebner's phenomenon (KP) has been observed in a number of skin diseases, including vitiligo. Its clinical significance in vitiligo with respect to disease activity and course is still debatable, while its relevance for surgical techniques has been demonstrated in some reports. We present a literature review on the currently known facts about KP in vitiligo, including details of clinical, experimental, and histopathological changes.

The haptenation theory of vitiligo and melanoma rejection: a close-up.

The 'Haptenation theory' concerns the multicausal pathogenesis of vitiligo ending ultimately in the (partial) disappearance of melanocytes from the skin and/or hairs. The melanocyte specificity is attributed to the tyrosinase-catalysed production of haptogenic ortho-quinones that covalently bind to tyrosinase or other melanosomal proteins to generate neo-antigens. These latter, in turn, trigger an immunological cascade resulting in a melanocyte-specific delayed-type hypersensitivity reaction that eliminates melanocytes and produces the characteristic depigmentation.

A reactive ortho-quinone generated by tyrosinase-catalyzed oxidation of the skin depigmenting agent monobenzone: self-coupling and thiol-conjugation reactions and possible implications for melanocyte toxicity.

Monobenzone (hydroquinone monobenzylether, 1) is a potent skin depigmenting agent that causes irreversible loss of epidermal melanocytes by way of a tyrosinase-dependent mechanism so far little understood. Herein, we show that 1 can be oxidized by mushroom tyrosinase to an unstable o-quinone (1-quinone) that has been characterized by comparison of its properties with those of a synthetic sample obtained by o-iodoxybenzoic acid-mediated oxidation of 1. Preparative scale oxidation of 1 with tyrosinase and catalytic l-DOPA, followed by reductive workup and acetylation, led to the isolation of two main products that were identified as the acetylated catechol derivative 4 and an unusual biphenyl-type dimer of 4, acetylated 5, arising evidently by coupling of 4 with 1-quinone.

Effect of one session of ER:YAG laser ablation plus topical 5Fluorouracil on the outcome of short-term NB-UVB phototherapy in the treatment of non-segmental vitiligo: a left-right comparative study.

Background: NB-UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year. Skin ablation with mechanical dermabrasion with 5Fluorouracil (5FU) was introduced to treat vitiligo in 1983. This was modified replacing the mechanical dermabrasion by erbium-YAG (ER:YAG) laser ablation and resulted in better prognosis in periungual vitiligo.

Vitiligo puzzle: the pieces fall in place.

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.

Evolutionary, biologic, and social aspects of skin color.

To understand the diversity of skin color now observed in people of the five continents, one has to go back in history. In fact, geology, archeological findings, biology and medical science, as well as anthropology, linguistics, and contemporary genetic techniques enable us to patch up a clear picture of the past up to the present - the evolution of the Homo sapiens. Owing to its undeniable visibility, skin color has always had a sociologic connotation, which has up to the present time caused division between people.

Progressive macular hypomelanosis: an overview.

Progressive macular hypomelanosis (PMH) is a common skin disorder that is often misdiagnosed. Various authors have written about similar skin disorders, referring to them by different names, but we believe that all these similar disorders are part of the same entity.PMH is characterized by ill-defined nummular, non-scaly hypopigmented spots on the trunk, often confluent in and around the midline, and rarely extending to the proximal extremities and neck/head region.

Benzoyl peroxide/clindamycin/UVA is more effective than fluticasone/UVA in progressive macular hypomelanosis: a randomized study.

Background: There is no effective treatment for progressive macular hypomelanosis. Recent findings indicate that Propionibacterium acnes may play a role in the pathogenesis.

Objectives: We sought to compare the effectiveness of antimicrobial therapy with anti-inflammatory therapy in patients with progressive macular hypomelanosis.

The discovery of the human melanocyte.

Around 2200 bc the first written description of a human pigmentation disorder, most likely vitiligo, was recorded, and from that moment the history of research into human pigmentation can be traced. For the following 4000 yr, the origins of human skin colour remained an enigma that was to generate a multitude of misconceptions. Even after European physicians began to dissect and compare dark and light coloured skin to reveal its underlying anatomy, the origins of skin and hair pigmentation were a matter of frequently erroneous speculation.

Noninvasive techniques for the evaluation of skin color.

Visual assessment remains one of the "gold standard" methods of assessing skin color and a number of tools are currently available to reduce the interobserver variability. Ultraviolet light examination remains a mainstay of the assessment of pigmentary disorders, while polarized light photography is useful for the appraisal of dermal changes, in particular those related to vascularity. With the introduction of modern instruments, reflectance spectroscopy using tristimulus colorimeters or narrowband spectrophotometers provides a convenient, objective, and reproducible methodology for the evaluation of pigmentation and skin color.

UVB 311 nm tolerance of vitiligo skin increases with skin photo type.

It is assumed that skin is protected against sunburn by melanin. In patients with vitiligo, there are white patches in the normal pigmented skin. We noticed that there is a difference in burning capacity of these white patches between people with different skin types.

Safety and efficacy of combined use of 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% solution and sunscreen in solar lentigines.

The objective of this open-label, noncontrolled study was to evaluate the safety of a combination solution containing 4-hydroxyanisole (mequinol) 2%/tretinoin 0.01% (Solagé) with a sunscreen in the treatment of solar lentigines. The study included a total of 406 subjects for a treatment period up to 24 weeks.

Difference in pathogenesis between vitiligo vulgaris and halo nevi associated with vitiligo is supported by an HLA association study.

Human leukocyte antigen (HLA) class II associations with two subtypes of vitiligo: vitiligo vulgaris and halo nevi associated with vitiligo were investigated. In previous studies associations between vitiligo and HLA antigens have been reported but these two subtypes have never been taken into account. However from a clinical and histological point of view, a difference in (auto)-immune pathogenesis can be expected.

Generalized mottled pigmentation with postnatal skin blistering in three generations.

We describe three generations of a family expressing progressive mottled hypopigmentation and hyperpigmentation on the non-exposed parts of the body from childhood to adult life. At birth, they all had epidermal blistering of the distal extremities. Although the palmoplantar warty keratoses could be related to the bulla formation, the pigmentary changes could not.

Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis.

Background: Progressive macular hypomelanosis is a common hypopigmentation mainly on the central parts of the trunk, predominantly in young adults, especially women. It is often mistaken for pityriasis versicolor and pityriasis alba. It occurs in all races and has been described in many parts of the world.

Increased epidermal functioning wild-type p53 expression in vitiligo.

Despite the lack of protective melanin and increased oxidative stress due to mM concentrations of epidermal H2O2 in vitiligo, there is no significantly increased risk for chronic actinic damage and non-melanoma skin cancer. Therefore the question arises, which protective mechanisms could be involved in the skin of these patients preventing the initiation of these cancers. Recently an overexpression of p53 has been shown in vitiligo.

Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo.

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the important role of cellular autoimmunity in the pathogenesis of this disease. We isolated T cells from both perilesional and nonlesional skin biopsies obtained from five vitiligo patients, then cloned and analyzed their profile of cytokine production after short-term, nonspecific expansion in vitro.

Gene expression patterns in melanocytic cells: candidate markers for early stage and malignant transformation.

Different stages of differentiation of human melanocytic cells, such as normal melanocytes, naevus and melanoma cells, reflect distinct gene expression patterns. A PCR-based subtractive hybridization and display method was applied to identify genes that are differentially expressed in melanocytic cells in relation to early stage and malignant transformation. This resulted in the identification of a number of candidate cDNAs differentially expressed among melanocytes, naevus cells, and (non)-metastatic melanoma cells.