Immunohistochemical Study of Vitamin D Receptor and β-catenin Expression in Alopecia Aerata and Androgenetic Alopecia

Abstract

SUMMARY A lopecia areata (AA) is an autoimmune disease that presents as well defined, usually rounded or oval patches of non-scarring hair loss with no overt epidermal changes. AA most commonly manifests as sudden loss of hair in well-demarcated, localized area in the scalp. Several different hypotheses for the pathogenesis of alopecia areata were suggested. Genetic factors seem to play an important role since there is a higher frequency of a family history in AA patients. Alopecia areata appears to have also an autoimmune factor causing the patient to develop antibodies to different hair follicle structures. Cytokines may play a role in alopecia areata by inhibiting hair follicle growth. Some studies show that emotional stress may also cause alopecia areata. Patients with congenital mutations in the VDR gene have a marked decrease in VDR expression and present with diffuse alopecia of varying severity, caused by loss of hair-cycle regulation. Androgenetic alopecia (AGA) is the most common hair loss disorder, affecting both men and women. It leads to progressive miniaturization of the hair follicle with a usually characteristic pattern of distribution in genetically predisposed men and women, there is progressive shortening of anagen, resulting in increased shedding of the short-lived hairs, while the follicles produce shorter, finer hairs. Androgens are major contributors of hair loss for the scalp. The canonical Wnt signaling pathway has been found to play an important role in follicle development. VDR, lymphoid enhancer factor (Lef1), and beta-catenin form a complex that activates the canonical Wnt pathway. However, the molecular mechanisms by which the VDR exerts these actions are not clear The vitamin D receptor (VDR), independent of vitamin D, plays an important role in hair cycling, specifically anagen initiation. VDR is a Wnt effector that controls hair follicle differentiation, and is directly involved in the regulation of the cWnt and hedgehog pathways during the hair cycle. The induction of cWnt and hedgehog target genes that characterizes early anagen and was found to be dramatically attenuated in VDR null mice. This work aimed to study vitamin D receptor and β-catenin expression in both alopecia aerata and androgenetic alopecia. This study included 100 subjects divided into three groups, the first group included 35 patients with AA, the second group included 35 patients with androgenic alopecia while the third control group included 30 healthy subjects. All patients were subjected to detailed history taking and examination to detect pattern, severity (SALT score) in patients with alopecia aerata, the Hamilton-Norwood’s score in case of male pattern androgenic alopecia, and Ludwig’s score in case of female androgenic alopecia.. Skin punch biopsy were taken from the lesional skin and stained with H & E to confirm the diagnosis and also immunohistochemically stained for Vitamin D receptor and β-catenin expression in patients with alopecia aerata and additionally for androgen receptor expression in patients with androgenetic alopecia. Skin biopsy from normal skin was also immune-stained by the three markers and then scoring of all the slides were done. The obtained data was tabulated and statistically analyzed. The results revealed that VDR and beta-catenin expression are significally reduced not only in hair follicles but also in the epidermis of patients with AA which could be related to the suppression of Wnt/β-catenin signals implying a role in of VDR in the pathogenesis of AA. Targeting the decreased VDR could be one of the therapeutic tools in the treatment of alopecia areata. Also there was positive association between both VDR score and staining intensity with β-catenin staining intensity in AA, confirming that decreased expression of VDR is related to suppression of the Wnt signalling pathway in AA.