Dysregulation of Circular Antigen-Specific T Cells Anergy in Autoimmune Vitiligo

Background: Vitiligo is an autoimmune disorder related to melanocyte loss;however, the exact interplay between antigen-specific autoimmunity and local oxidative stress remains unclear. Recently, the migration ability and number of Foxp3-expressing regulatory T cells (Tregs) in lesional skin was found to be reduced in vitiligo patients. Objectives: We aimed to clarify the T cell anergy status of melanocytes by focusing on the impaired equivalence of peripheral melanocyte-specific cytotoxic T cells and functional Tregs in patients with progressive vitiligo. Materials and methods: Ten progressive vitiligo patients and 10 age-matched healthy individuals were enrolled in this study. We analyzed the number of functional Tregs in progressive vitiligo patients and compared the findings with those of controls. Next, to assess the suppressive activity of Tregs on melanocyte-specific T lymphocytes, we strictly purified the functional Tregs fraction and Melan-A-specific CD8+ T cells and co-cultured these cells with each other. The number of Melan-A-specific CD8+ T cells was then counted by FACS. In addition, the expression of the representative exhaustion markers PD-1 and CTLA-4 on functional Tregs was assessed in vitiligo patients and normal controls. Results: The number of functional Tregs itself was not significantly decreased in the blood of vitiligo patients compared to healthy controls. However, the cytotoxic T cell (CTL) proliferation was significantly decreased after cultivation with Tregs from healthy individuals (p < 0.01), and this decrease in CTLs was less marked after cultivation with Tregs from vitiligo patients. Conclusions: We demonstrated a reduced suppressive function of activated Tregs on Melan-A-specific CTLs in the circulating cells of vitiligo patients compared with healthy controls. This result suggests that T cell anergy with Tregs dysfunction may participate in the immune response to melanocytes in vitiligo patients.

Preliminary Colorimetric Assessment of Progressive Nonsegmental Vitiligo under Short-Term Intravenous Methylprednisolone Pulse Therapy

Although the administration of systemic steroid for nonsegmental vitiligo in the progressive stage is a recommended treatment according to guidelines, the clinical efficacy of this regimen has not been fully established. In this study, we evaluated the clinical efficacy of half-dose steroid treatment and stratified the evidence regarding its usefulness in progressive vitiligo patients. Half-dose steroid pulse therapy (500 mg/day of methylprednisolone for three sequential days) was administered intravenously three times monthly in five vitiligo patients. The visual changes in vitiligo lesions were evaluated on photographs and quantified using a spectrophotometer. As results, all patients completed three cycles of treatment without severe adverse events. Three of the five patients achieved disease arrest with decrease in white contrast. Therefore, short-term and halfdose steroid therapy is well tolerated and effective for achieving disease arrest in progressive nonsegmental vitiligo. The whiteness assessed by a spectrophotometer is possibly associated with therapeutic response to steroid therapy.