effect of nb-uvb on the tissue level of il 15 and il-15rα in active non segmental vitiligo cases.

Conditions: Active Non Segmental Vitiligo

Summary: this study aims at evaluating the effect of nb-uvb on tissue level of il-15 and il-15 receptor alpha subunit (il-15rα)(cd215) in active non segmental vitiligo. this in turn will shed light on the potential role of phototherapy as a safe mean of prevention of vitiligo recurrence as well as evaluating the utility of il 15 and il 15 rα as markers of vitiligo activity/recurrence.

vitiligo is a t cell-mediated, autoimmune cutaneous disorder characterized by loss of functioning melanocytes from the basal layer of epidermis and/or hair follicles, leading to depigmented areas of the skin, mucous membranes, and/or hair (strassner et al., 2018). multiple factors have been involved in disease development, with a prominent role of the immune system, in particular t cells. after repigmentation, vitiligo usually recurs in the same area, drawing attention to the fact that resident memory t cells (trm) are present at the sites of vitiligo lesions. this was confirmed by a number of studies (boniface et al., 2018 , boniface\& seneschal., 2019 , riding\& harris., 2019) showing that stable and active vitiligo perilesional skin is enriched with a population of cd8 trm expressing both cd69 and cd103. cd8 trm expressing cd103 are localized mainly in the epidermis. il-15 is the only identified cytokine required for maintenance of cd8 trm cells (baumann et al., 2018 and richmond et al., 2018). interleukin 15(il-15) is one of interleukin 2(il-2) family members. it plays an important function in the pathogenesis of multiple cutaneous autoimmune diseases as psoriasis (rückert et al.,2000) , alopecia areata (ebrahim et al.,2019) and vitiligo (atwa et al.,2020). il-15 receptor (il-15r) is expressed on natural killer cells, dendritic cells, monocytes, fibroblasts, t cells and keratinocytes . il-15r is composed of α (cd215), β (cd122), and γ (cd132) chains , the alpha chain occurs as both a soluble and a membrane-attached subunit (vámosi et al., 2004 , budagian et al., 2006 and di sabatino et al.,2011). il-15 stimulates neighbor cells by a trans-presentation mechanism through secretion of (il-15. il-15rα complexes) from the surface of monocytes or dendritic cells into endosomes for its presentation in trans to neighboring cytotoxic cells or natural killer cells ( stonier \& schluns .,2010). il-15 enhances maturation and survival of natural killer (nk) cells, neutrophils, and dendritic cells (dcs) (di sabatino et al.,2011). additionally, il-15 promotes nk cell cytotoxicity and cytokine production such as interferon gamma( ifn-γ )and tumour necrosis factor alfa (tnf-α) (fehniger \& caligiuri .,2001). as for dcs, they regulate the development and survival of memory cytotoxic cells by il-15 trans-presentation ( budagian et al., 2006 and stonier \& schluns.,2010). furthermore, il-15 promotes t-cell receptor-dependent proliferation of th17 (di sabatino et al.,2011). trm primarily express the cd122 (il-15r β) subunit, a shared component of the receptors for il-2 and il-15, whereas keratinocytes express more cd215(il-15rα) in lesional compared to non lesional skin which is consistent with an ability to present il-15 to t cells in trans (richmond et al., 2018). cd122(il-15r β) expression is significantly higher on melanocyte-specific t cells in both mouse and human vitiligo compared to endogenous memory t cells, suggesting that autoreactive t cells are more dependent on il-15 than non-autoreactive t cells. in addition, anti-cd122 blocking antibody inhibit il-15 mediated t cell survival but not il-2-mediated proliferation in vitro. this is consistent with the role of il-15 in mediating t cell survival, but not proliferation (riding et al., 2018). these findings are consistent with an important role of il-15 in maintenance of autoreactive trm cells in vitiligo and suggest that this could be an effective targeted treatment strategy for vitiligo patients ( frisoli et al., 2020). phototherapy has been considered as a cornerstone in management of vitiligo patients (esmat et al., 2017). narrow band ultraviolet b (nb-uvb) has been found to be an effective and well-tolerated treatment option in vitiligo compared to other available photo(chemo)therapy options (sokolova et al., 2015). regarding effect of ultraviolet b treatment on il-15 in normal skin, it was found to increase il-15 expression in epidermal and dermal sheets as well as in cultured keratinocytes and dermal fibro-blasts (mohamadzadeh et al.,1995). however, this was negated by blauvet et al. in 1996 who proved that il-15 expression is down regulated by uvb in cultured keratinocytes in a dose and time dependent manner (blauvet et al., 1996).

Eligibility criteria:
inclusion criteria: * age: ≥ 18 years. * both genders. * type of vitiligo: non segmental vitiligo (nsv). * active disease for less than 6 months (vida ≥ +2). * no systemic or topical treatment for vitiligo for at least one month. exclusion criteria: * patients less than 18 years. * vida ≤ +1. * contraindications to phototherapy (precancerous conditions like * xeroderma pigmentosum , photosensitivity, history of arsenic intake, * ionizing radiation, extensive previous exposure to puva, patients * with a history of melanoma, atypical nevi, non-melanoma skin * cancers and patients taking immunosuppressive medications ( menter et al., 2010 and mehta \& lim, 2016). * pregnancy and lactation . * patients who received systemic or topical treatment for the past * month. * patients having any autoimmune diseases .