الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Vitiligo is a common, acquired depigmentation disorder characterized by chronic white asymptomatic macules and patches, due to selective loss of functional melanocytes of the skin. The striking visual contrast between the normal pigmented and lesional skin causes psychological and social stigma in most of patients, which can be devastating on darker skin phototypes.
Vitiligo is a multifactorial disorder and numerous hypotheses have been proposed to explain it. Yet, the exact pathogenesis of vitiligo remains inscrutable. It had been agreed that T-cell mediated melanocyte destruction is the final step in its pathogenesis regardless the initiating steps. Cytotoxic CD8+ T cells infiltrate the skin of vitiligo patients, and are able to recognize and kill melanocytes. Induction and activation of these cytotoxic CD8+ T cells and loss of tolerance to melanocyte autoantigens in vitiligo are not clear, however it seems likely due to some defects in Tregs.
CTLA-4 and PD-1 are immune checkpoints capable of down-regulating T-cell immune functions and halting the immune response, thus preventing unwanted inflammatory response and safeguarding against autoimmunity.
PD-1 is expressed on the T cells, B cells, and macrophages. Its ligands include PD-L1 and PD-L2; PD-L1 is expressed by melanoma cells and melanocytes within an inflammatory milieu, whereas PD-L2 is expressed on APCs. On the other hand, CTLA-4 is expressed by activated T-cells, and interacts with B7 on the APCs.
Neutralization of these inhibitory molecules, PD-1 and CTLA-4, by antibodies has proven to be effective therapy against metastatic melanoma and other cancers. Unfortunately, vitiligo-like lesions have been reported as a side effect of these therapies which could refer to a possible role of these immune checkpoints in melanocytes tolerance.
This prospective cross-sectional study aimed to investigate the possible pathogenic roles of PD-1 and CTLA-4 in vitiligo. This may shed the light on a new aspect in the enigmatic pathogenesis of vitiligo, and provide a possible new strategy in its treatment.
The study concluded that CTLA-4 and PD-1 pathways may be implicated in the pathogenesis of vitiligo. PD-1 may cause exhaustion of CD4+ T cells unleashing autoreactive cytotoxic T cells in activity, or exhaustion of cytotoxic T cells halting its destructive capacity in stability. On the other hand, defective CTLA-4 pathway may lead to failed CTLA-4-mediated inhibition with subsequent anti-melanocytic immune response. However, their pathogenic roles in vitiligo need to be more elucidated by more studies on larger samples that include active and stable cases. Furthermore, determining the exact T cell subtype that express PD-1 or CTLA-4, using double-staining procedures, seems to be a good method to understand the role of these immune checkpoints in vitiligo.