CDH1 and DDR1 common variants confer risk to vitiligo and autoimmune comorbidities

Almasi‐Nasrabadi, Mina; Amoli, Mahsa M.; Robati, Reza M.; Rajabi, Fateme; Ghalamkarpour, Fariba; Gauthier, Yvon

doi:10.1016/j.gene.2019.03.026

Cited by 13 publications

(9 citation statements)

References 20 publications

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“…showed hands and feet were affected. This was in accordance to [27] different from another study of [5] and [28] that there was no significant correlation.…”

Section: Multiple Mechanismssupporting

confidence: 81%

Expression of E-cadherin in Vitiligo Patients before and after Narrow Band UVB

Refaie

Gaber

Abdellatif

2022

Egyptian Journal of Medical Research

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Background: Vitiligo is the most common chronic acquired depigmenting disorder, resulting from the loss of melanocytes from the basal epidermal layer . Ecad is the major adhesion molecule mediating melanocyte-keratinocyte interactions and is essential for both the establishment of epithelial structures during development and numerous dynamic pro-cesses such as differentiation, polarity, proliferation, and migration during morphogenesis and homeostasis. The aim of this work : is to estimate the level of E-cadherin in serum of vitiligo patients before and after NB-UVB therapy as compared to normal control persons, to evaluate the role of E-cadherin in the pathogenesis of this disease . Patients and methods: The level of Ecadherin was detected in 30 venous blood samples of vitiligo patients before (group I) and after treatment with NB-UVB ( group II) and 30 healthy controls using ELISA. Informe consent was obtained from the participants in this study after ethical committee approval from Dermatology Department of Medicine, Beni Suef University . Results: Serum level of E-cadherin was significantly higher in vitiligo patients before exposure to narrow band UVB compared to healthy controls and became lower in vitiligo patients after exposure to narrow band UVB but still higher than control. No detected relation was found between serum level of E-cadherin and patients' age, skin type, symmetry ,vitiligo type ,last time of new lesions and VIDA (p-value >0.05). In addition, Serum Level of E-cadherin was significantly higher in Vitiligo patients with negative as compared with positive family history; with a statistically significant (p-value= 0.045),and slight negative significant linear correlation between serum level of E-cadherin and percentage of vitiligo in studied Vitiligo patients; (p=0.045). Coclusion :E-cadherin may play arole in the pathogenesis of vitiligo.Recommendations: On the basis of our findings in this study and in conjunction with that from previous studies, we suggest that: 1) Additional studies on large number of cases in association with assessment of E-cadherin to evaluate its exact role in vitiligo pathogenesis. 2) Study gene polymorphism of E-cadherin gene and association with vitiligo. 3) Performing experimental study to evaluate the effect of E-cadherin up-regulation on vitiligo patients' response to NB-UVB and other modalities of therapy.

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“…showed hands and feet were affected. This was in accordance to [27] different from another study of [5] and [28] that there was no significant correlation.…”

Section: Multiple Mechanismssupporting

confidence: 81%

Expression of E-cadherin in Vitiligo Patients before and after Narrow Band UVB

Refaie

Gaber

Abdellatif

2022

Egyptian Journal of Medical Research

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“…The encoding proteins or corresponding function of some susceptibility genes identified by GWAS still remains unknown, including FARP2-STK25, FBXO45-NRROS, SCAF1-IRF3-BCL2L12, and ZC3H7B-TEF [101]. Besides, candidate gene studies showed polymorphisms in genes that promote cell adhesion (CDH1, DDR1) also conferring risk to vitiligo, which were warranted to be confirmed by GWAS results [1,104,105]. These genetic bases of vitiligo support that innate immunity and adaptive immunity are implicated in the disease and exert harmful efforts on melanocytes.…”

Section: Genetic Background Of Vitiligo and Its Relationship To Immune Functionmentioning

confidence: 98%

Clinical Features, Immunopathogenesis, and Therapeutic Strategies in Vitiligo

Wang

2021

Clinic Rev Allerg Immunol

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Vitiligo is an autoimmune disease of the skin characterized by epidermal melanocyte loss resulting in white patches, with an approximate prevalence of 0.5-2% worldwide. Several precipitating factors by chemical exposure and skin injury present commonly in patients with vitiligo. Although the diagnosis appears to be straightforward for the distinct clinical phenotype and specific histological features, vitiligo provides many challenges including chronicity, treatment resistance, frequent relapse, associated profound psychosocial effect, and negative impact on quality of life. Multiple mechanisms are involved in melanocyte disappearance, including genetics, environmental factors, and immune-mediated inflammation. Compelling evidence supports the melanocyte intrinsic abnormalities with poor adaptation to stressors leading to instability and release of danger signals, which will activate dendritic cells, natural killer cells, and innate lymphoid cells to initiate innate immunity, ultimately resulting in T-cell mediated adaptive immune response and melanocyte destruction. Importantly, the cross-talk between keratinocytes, melanocytes, and immune cells, such as interferon (IFN)-γ signaling pathway, builds inflammatory loops that give rise to the disease deterioration. Improved understanding of the immune pathogenesis of vitiligo has led to the development of new therapeutic options including Janus kinase (JAK) inhibitors targeting IFN-γ signaling pathways, which can effectively reverse depigmentation. Furthermore, definition of treatment goals and integration of comorbid diseases into vitiligo management have revolutionized the way vitiligo is treated. In this review, we highlight recent developments in vitiligo clinical aspects and immune pathogenesis. Our key objective is to raise awareness of the complexity of this disease, the potential of prospective therapy strategies, and the need for early and comprehensive management.

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“…STAT3 may be modulated by arsenic trioxide in treatment-naïve patients with rheumatoid arthritis and may improve the Treg/Teff balance (29). STAT3 has been detected in VIT pathogenesis (30), but the association between STAT3 modulation and Treg/Teff balance in VIT is less explored.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑21‑5p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo

Huo

Liu

et al. 2020

Mol Med Rep

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Vitiligo (VIT) is caused by loss and degradation of functional epidermal melanocytes. Studies have indicated that melanocyte destruction may be associated with an imbalance between regulatory T cells (Treg cells) and effector T cells (Teff cells). The current study aimed to investigate the molecular mechanism through which Treg/Teff balance affects VIT pathogenesis. To explore this, peripheral blood mononuclear cells were isolated from patients with VIT and healthy individuals. The present study revealed that the proportions of CD4 + T cells, Treg cells and T helper 1 (Th1) cells were decreased in patients with VIT, but those of Teff cells (Th17 and Th22 cells) were increased; additionally, Foxp3 expression was decreased, but the expression levels of interferon-γ, interleukin (IL)-17A and IL-22 were increased. Furthermore, in patients with VIT, microRNA (miR)-21-5p expression was decreased, while that of STAT3 was increased. Further in vitro experiments in CD4 + T cells revealed that STAT3 was targeted by miR-21-5p. Functional analysis further indicated that miR-21-5p overexpression in Th17-polarized CD4 + T cells decreased the proportion of Teff cells and associated cytokines, such as IL-17A and IL-22, but increased the proportion of Treg cells and Foxp3. However, the effects of miR-21-5p overexpression were partly reversed by STAT3 overexpression. Increased apoptosis of melanocytes was detected after co-culture with Th17-polarized CD4 + T cells in the presence of a miR-21-5p mimic. However, this indirect effect of the miR-21-5p mimic on melanocytes was decreased via STAT3 overexpression. Therefore, miR-21-5p may protect melanocytes via targeting STAT3 and regulating Treg/Teff balance. The current findings may provide a possible treatment method for managing VIT.

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CDH1 and DDR1 common variants confer risk to vitiligo and autoimmune comorbidities

Cited by 13 publications

References 20 publications

Expression of E-cadherin in Vitiligo Patients before and after Narrow Band UVB

Expression of E-cadherin in Vitiligo Patients before and after Narrow Band UVB

Clinical Features, Immunopathogenesis, and Therapeutic Strategies in Vitiligo

MicroRNA‑21‑5p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo

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