Immunopathogenesis of vitiligo
Immunopathogenesis of vitiligo Vitiligo vulgaris is an acquired skin disorder characterized by expanding white lesions of the skin. This depigmentation of the skin is due to the disappearance of pigment cells (melanocytes). We and others have shown that immune reactions against melanocytes are responsible for the disappearance of melanocytes in vitiligo patients. These immune reactions consist of activated T lymphocytes in the vitiligo skin. These lymphocytes are also found in the blood, allowing spreading of the immune reactions. Moreover, autoantibodies against melanocyte antigens are found in vitiligo patients. Our research was published in the Journal of Investigative Dermatology in 2009.
Treatment of vitiligo
Vitiligo patients can be treated with UVB radiation and/or transplantation of normal pigmented skin (autologous skin minigrafting), which are currently available at the Netherlands Institute for Pigment Disorders of the AMC. UVB is known to suppress the immune system in the skin. We are currently investigating how this immunesuppression leads to repigmentation of the vitiligo skin.
Vitiligo and immunotherapy of melanoma
Melanoma is an aggressive form of skin cancer that arises from melanocytes. It is relatively insensitive to standard cancer treatments and therefore difficult to treat. Melanoma cell can however be detected by the immune system, leading to anti-melanoma immunity. This so-called immunogenic character of melanoma forms the basis of immunotherapy. Immunotherapy aims at stimulating anti-melanoma immune responses in patients to attack melanoma cells and induce tumor regression. During immunotherapy patients may develop vitiligo. This is associated with an improved prognosis. (published in Teulings et al. J. Clin oncology 2015). In these patients, the anti-melanoma immune response also attack normal melanocytes.
MI therapy and MIC therapy for melanoma
Based on our research on the pathogenesis of vitiligo, we developed a new form of immunotherapy of melanoma, consisting of the vitiligo-inducing/skin-bleaching compound monobenzone, combined with immunostimulating adjuvants Imiquimod and/or CpG (MI therapy and MIC therapy). This therapy proved very effective in treating the aggressively growing B16 melanoma in vivo. MIC therapy also induced long-term immunological memory that prevented tumor outgrowth after completion of therapy. Importantly, we discovered a new immunological mechanism of how the chemical compound monobenzone induces anti-melanocyte/melanoma immunity. This research was published in PLoS one and Journal of Investigative Dermatology.
Clinical trial of MI therapy
Based on our results, MI therapy has been tested clinically in melanoma patients at the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam. Results will be published in an international oncology journal.
Immunopathogenesis of atopic dermatitis
Atopic dermatitis (AD) is a multifactorial, itchy, chronic inflammatory skin disease affecting 15-30% of the children and 2-10% of the adult Caucasian population with a substantial negative impact on patients` quality of life. It belongs to the top 5 of most common skin disorders. Several factors that can trigger AD have been identified, such as inhaled allergens, food allergens and microorganisms that can infect skin. How exactly these factors influence AD is unknown. Our research focusses on understanding the pathogenesis of the inflammatory response in AD, involving both cellular and humoral immunity. This knowledge will provide new targets for therapeutic intervention in AD.
This research is performed at department of Dermatology of the AMC (Head: prof dr. R. Hoekzema and prof dr. M.A. de Rie, former head prof. dr. J.D. Bos) and the Netherlands Institute for Pigment Disorders (dr. A. Wolkerstorfer, MD PhD, dr. M.W. Bekkenk, MD PhD and former head SNIP: Dr. J.P.W. van der Veen, MD PhD) in collaboration with Prof. dr. C.J. Melief, MD PhD (Leiden University Medical Center), The Antoni van Leeuwenhoek Netherlands Cancer Institute and the VU University Medical Center.
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