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    Association between TAP1 gene polymorphisms and alopecia areata in a Korean population. Kim H K,Lee H,Lew B L,Sim W Y,Kim Y O,Lee S W,Lee S,Cho I K,Kwon J T,Kim H J Genetics and molecular research : GMR The transporter 1 ATP-binding cassette sub-family B (MDR/TAP) gene (TAP1) is located in the major histocompatibility complex class II region, and forms a heterodimer that plays a key role in endogenous antigen presentation pathways. Investigation of polymorphisms identified in these loci has revealed an association with several autoimmune disorders. Alopecia areata (AA) is a common autoimmune disease resulting from T cell-induced damage to hair follicles. The present study documents for the first time a comparison between the allelic and genotypic frequencies of TAP1 single nucleotide polymorphisms (SNPs) in patients with AA and those of a control group, using a direct sequencing method. Our results suggest an association between a promoter SNP (rs2071480) and susceptibility to this disease. 10.4238/2015.December.28.31
    Correlation of vitamin D and vitamin D receptor expression in patients with alopecia areata: a clinical paradigm. Daroach Manju,Narang Tarun,Saikia Uma N,Sachdeva Naresh,Sendhil Kumaran Muthu International journal of dermatology BACKGROUND:Vitamin D (Vit.D) deficiency has been reported in alopecia areata (AA). Downregulation of Vitamin D receptor (VDR) on hair follicles is associated with reduced hair growth. OBJECTIVE:To correlate serum Vit.D levels with severity, pattern, and duration of AA, and density of VDR expression over hair follicles in AA patients. METHODS:Prospective study including 30 AA patients and 30 healthy controls. Clinical details and serum Vit.D measurement and scalp biopsy for histopathology and VDR expression was performed in patients and controls at baseline and after 6 months of treatment of AA. RESULTS:Mean age of patients and controls was 28.9 ± 9.96 and 31.17 ± 9.43 years, respectively. Mean SALT score in patients was 35.8 ± 27.5 with a median disease duration of 48 weeks. Mean serum Vit.D levels was 7.65 ± 4.50 ng/ml and 15.8 ± 11.47 ng/ml in patients and controls, respectively. Twenty-nine (96.7%) patients were Vit.D deficient (<20 ng/ml), compared to 22 (73.3%) controls (P = 0.001). Serum Vit.D levels inversely correlated with severity of the disease (r = -256), P = 0.17, and duration of disease but did not correlate with pattern of AA and VDR expression in tissue samples. VDR expression was reduced in all patients and was normal in controls. Inverse correlation of VDR was noted with presence of inflammation on histology (P = 0.02). VDR upregulation post treatment was seen only in 13% of patients and demonstrated no correlation with response to treatment. CONCLUSION:Vit.D deficiency in AA correlates inversely with disease severity and duration. VDR expression is reduced in AA and inversely correlate with inflammation histologically but does not correlates with serum Vit.D levels, severity, pattern, or duration of illness. 10.1111/ijd.13851
    The autoimmune basis of alopecia areata: a comprehensive review. Islam Naseeha,Leung Patrick S C,Huntley Arthur C,Gershwin M Eric Autoimmunity reviews Alopecia areata (AA) is a common, non-scarring dermatologic condition regularly distinguished by patches of hair loss on the scalp also manifesting in other, severe forms, including alopecia totalis (total loss of hair on the scalp) and alopecia universalis (complete loss of hair on the scalp and body). AA is a clinically heterogeneous disease with greatly varying yet typical symptoms, but the etiology for AA remains an enigma. However, clinical and experimental studies have pointed to autoimmune involvement, specifically regarding immune privilege sites of the hair follicles and the infiltration of CD4+ and CD8+ T cells and a predominant Th1 cytokine profile. Environmental insults, such as viral infections, trauma and genetic predisposition are also believed to contribute to the disease process. Multiple treatment options including the use of broad acting corticosteroids appear to be relatively effective in mild cases, however the clinical management of more severe forms of AA is much more difficult. Recent studies suggest that intervention of the JAK pathway may have a potential therapeutic efficacy for AA. 10.1016/j.autrev.2014.10.014
    Role of T helper 17 cells and T regulatory cells in alopecia areata: comparison of lesion and serum cytokine between controls and patients. Loh S-H,Moon H-N,Lew B-L,Sim W-Y Journal of the European Academy of Dermatology and Venereology : JEADV BACKGROUND:Alopecia areata (AA) is an organ-specific autoimmune disease with T-cell-mediated attack of hair follicle autoantigens. As T helper 17 (Th17) cells and T regulatory (Treg) cells are crucially involved in the pathogenesis, the role of Th17 and Treg cytokines has not been studied yet. OBJECTIVE:To determine whether AA is associated with alterations in lesional and serum Th17 and Treg cytokines and studied whether they were associated with clinical type. METHODS:Scalp skin samples from 45 patients and eight normal controls were obtained for PCR specific for IFN-γ, TNF-α, TGF-β, IL-1, IL-2, IL-4, IL-10, IL-12A, IL-13, IL-17, IL-22 and IL-23. Serum cytokines were measured from 55 patients and 15 normal controls using ELISA. RESULTS:Lesional IL-17 and IL-22 were significantly increased in patient group. Moreover, positive correlations were shown between lesional IL-17, IL-22 and disease severity. Serum IL-1, IL-17, TNF-α and TGF-β were significantly increased, and positive correlation was shown between serum IL-17 and disease severity. CONCLUSION:These results showed significantly high Th17 cytokines in both lesion and serum in AA patients, which may highlight a functional role of these cytokines in the pathogenesis of AA. 10.1111/jdv.14775
    Serum vitamin D level is related to disease severity in pediatric alopecia areata. Unal Mehmet,Gonulalan Gulsum Journal of cosmetic dermatology BACKGROUND:Alopecia areata (AA) is the most common cause of inflammatory hair loss. AA is considered an autoimmune disease and occurs with various autoimmune disorders. Recent studies have revealed connection between autoimmune diseases and vitamin D deficiency. OBJECTIVES:In this study, we investigated vitamin D status in AA and its relationship with disease severity, number of patches, and disease duration. METHODS:This study included 20 pediatric patients with AA and 34 pediatric healthy controls. The serum vitamin D levels were evaluated. RESULTS:The mean serum 25(OH)D concentration of patients was 15.47±7.66 ng/mL and of control group was 11.09±10.53 ng/mL. There was no statistically significant difference between two groups (P: .084). Vitamin D concentration had significantly and negatively correlated with SALT score (P<.001 and r: -.831), number of patch (P<.001 and r: -.989), and disease duration (P<.001 and r: -.997). CONCLUSION:Vitamin D deficiency is not the only etiologic factor in AA pathogenesis, but in the presence of other etiological factors, this deficiency can aggravate AA severity, and thus, vitamin D supplementation may be beneficial in treatment of pediatric AA. 10.1111/jocd.12352
    The genetics of alopecia areata: new approaches, new findings, new treatments. Biran Roni,Zlotogorski Abraham,Ramot Yuval Journal of dermatological science Alopecia areata (AA) is a common immune-mediated hair loss disorder. Despite its high prevalence, its etiology is still largely unknown, but it is hypothesized to have a strong genetic basis. In the last decade, there has been a major progress in the field of genetic research, leading to novel findings regarding the genetic component of AA. The aim of this review is to summarize the information collected so far in this field, the basic principles of the genetic methods used in previous studies, and new therapeutic strategies that might become available in light of the new findings. 10.1016/j.jdermsci.2015.01.004
    Vitamin D Deficiency in Alopecia Areata. Ghafoor Rabia,Anwar Muhammad Irfan Journal of the College of Physicians and Surgeons--Pakistan : JCPSP OBJECTIVE:To compare the mean Vitamin D level in patients with alopecia areata (AA) with age and gender controlled matched healthy controls. STUDY DESIGN:Case-control study. PLACE AND DURATION OF STUDY:Dermatology OPD, JPMC, from October 2014 to March 2015. METHODOLOGY:All the patients diagnosed of alopecia areata by a trained dermatologist were selected. Controls were age and gender matched healthy volunteers. Venous blood was drawn and sent to hospital laboratory for 25 (OH) vitamin D by enzyme immunoassay method on chemical analyser. Data was recorded on SPSS version 16. Mann-Whitney test was applied to compare vitamin D levels of cases and controls. P-value <0.05 was taken as significant. RESULTS:There are 30 cases of AA, and 30 age and gender matched controls. The mean age of our study group was 23.77 ±8.86 ng/dL in patients and 24.03 ±8.62 ng/dL in the control group. Fifteen (50%) patients presented between 3-12 months of onset of AA. Median (IQR) vitamin D level of cases was 13.5 (18.6) ng/dL and healthy controls was 22.5 (16.25) (p=0.001). CONCLUSION:Serum Vitamin D levels were significantly lower in patients with alopecia areata compared to healthy controls. 2589
    The Role of Micronutrients in Alopecia Areata: A Review. Thompson Jordan M,Mirza Mehwish A,Park Min Kyung,Qureshi Abrar A,Cho Eunyoung American journal of clinical dermatology Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune-mediated attack of the hair follicle. As with other immune-mediated diseases, a complex interplay between environment and genetics is thought to lead to the development of AA. Deficiency of micronutrients such as vitamins and minerals may represent a modifiable risk factor associated with development of AA. Given the role of these micronutrients in normal hair follicle development and in immune cell function, a growing number of investigations have sought to determine whether serum levels of these nutrients might differ in AA patients, and whether supplementation of these nutrients might represent a therapeutic option for AA. While current treatment often relies on invasive steroid injections or immunomodulating agents with potentially harmful side effects, therapy by micronutrient supplementation, whether as a primary modality or as adjunctive treatment, could offer a promising low-risk alternative. However, our review highlights a need for further research in this area, given that the current body of literature largely consists of small case-control studies and case reports, which preclude any definite conclusions for a role of micronutrients in AA. In this comprehensive review of the current literature, we found that serum vitamin D, zinc, and folate levels tend to be lower in patients with AA as compared to controls. Evidence is conflicting or insufficient to suggest differences in levels of iron, vitamin B, copper, magnesium, or selenium. A small number of studies suggest that vitamin A levels may modify the disease. Though understanding of the role for micronutrients in AA is growing, definitive clinical recommendations such as routine serum level testing or therapeutic supplementation call for additional studies in larger populations and with a prospective design. 10.1007/s40257-017-0285-x
    Regulatory T-cells in alopecia areata. Speiser Jodi J,Mondo Dana,Mehta Vikas,Marcial Sheela A,Kini Ameet,Hutchens Kelli A Journal of cutaneous pathology BACKGROUND:Alopecia areata (AA) is believed to have an autoimmune mechanism in which the hair follicles are targeted by CD4+ and CD8+ lymphocytes. Studies investigating the autoimmune mechanism of other cutaneous diseases, including vitiligo, showed that T is a component of cutaneous immune privilege. Our study uses immunohistochemical staining in formalin-fixed, paraffin-embedded tissue to examine the percentage of CD4 FoxP3 , CD25 FoxP3 , and CD8 FoxP3 T in AA in human specimens. METHODS:Immunohistochemical double staining for CD4 FoxP3 , CD25 FoxP3 , and CD8 FoxP3 was performed on 12 AA cases and 12 other autoimmune and non-autoimmune cutaneous diseases. The frequency of CD4 FoxP3 , CD25 FoxP3 , and CD8  FoxP3 T was counted and expressed as a percentage of total CD4 , CD25 , and CD8 lymphocytes, respectively, in order to account for intersample inflammatory response variability. RESULTS:There was a significant reduction in the mean frequency of CD4  FoxP3 and CD25  FoxP3 in AA when compared to other autoimmune and non-autoimmune cutaneous diseases. CONCLUSION:T is significantly lower in AA when compared to other cutaneous diseases. Additionally, this immunohistochemical-staining protocol may be useful to evaluate T in formalin-fixed, paraffin-embedded specimens for other cutaneous diseases. Studies examining T in AA and other cutaneous diseases may have implications for future interventions. 10.1111/cup.13479
    Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations. Czarnowicki T,He H Y,Wen H-C,Hashim P W,Nia J K,Malik K,Estrada Y,Kimmel G W,Taliercio M,Krueger J G,Guttman-Yassky E Allergy BACKGROUND:Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA ) vs systemic (CLA ) "polar" CD4 and CD8 and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. METHODS:Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4 and CD8 T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls. RESULTS:AA patients had increased CLA /CLA Th2 (P < .007), CLA Tc2 (P = .04), and CLA Th22 (P < .05) frequencies than controls. Except of CLA Tc1 cells (P = .03), IFN-γ levels were mostly similar between AA, AD, and controls (P > .1). ICOS and HLA-DR activation were significantly higher in AA than controls (P < .05). T regulatory cells were significantly decreased in AA patients than controls (P < .01) and were correlated with activated CD8 T cells and with multiple cytokine subsets (P < .05). While Th2 and Tc2 clustered with disease severity, IFN-γ producing cells were linked with AA duration. CONCLUSIONS:Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients. 10.1111/all.13346
    Alopecia areata. Pratt C Herbert,King Lloyd E,Messenger Andrew G,Christiano Angela M,Sundberg John P Nature reviews. Disease primers Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future. 10.1038/nrdp.2017.11
    Correlation between serum IL-17A level and SALT score in patients with alopecia areata before and after NB-UVB therapy. Morsy Hanan,Maher Reham,Negm Dalia Journal of cosmetic dermatology BACKGROUND:There is strong evidence that alopecia areata is of immunological background; Interleukin-17 (IL-17) is a Th17 pro-inflammatory cytokine that has been allied to the pathogenesis of different autoimmune and inflammatory diseases. OBJECTIVE:This study aimed to measure serum IL-17A in patients with alopecia areata, and to study associations between IL-17A levels and disease severity before and after Narrowband-Ultraviolet B (NB-UVB), patient gender and age. METHODS:Twenty patients with AA of the scalp were treated with (NB-UVB), and 15 healthy subjects' age and sex matched were enrolled as controls. Patients were assessed clinically by SALT score. Assay of serum levels of IL-17A by ELISA was done in patients and controls. RESULTS:The mean level of IL-17A was (15.63 Â ± 10.89 Pg/mL) in AA patient group, and (16.50 Â ± 5.02 Pg/mL) in control group. No statistically significant correlation was detected between SALT score and IL-17A level before (NB-UVB) treatment while a significant negative correlation between SALT score and IL-17A level was observed after treatment (r = -.448, P = .047). Mean SALT score for patients was (14.03 Â ± 13.48), and correlated positively with age (r = .446, P = .049). CONCLUSION:Although (NB-UVB) is an immune-modulatory type of treatment for alopecia areata of mild efficacy especially if it's used alone, it has shown significant decrease in serum IL-17A level among patients, and correlation to disease severity. 10.1111/jocd.12664
    Objective outcome measures: Collecting meaningful data on alopecia areata. Olsen Elise A,Roberts Janet,Sperling Leonard,Tosti Antonella,Shapiro Jerry,McMichael Amy,Bergfeld Wilma,Callender Valerie,Mirmirani Paradi,Washenik Ken,Whiting David,Cotsarelis George,Hordinsky Maria Journal of the American Academy of Dermatology BACKGROUND:Although alopecia areata is a common disorder, it has no US Food and Drug Administration-approved treatment and evidence-based therapeutic data are lacking. OBJECTIVE:To develop guidelines for the diagnosis, evaluation, assessment, response criteria, and end points for alopecia areata. METHODS:Literature review and expert opinion of a group of dermatologists specializing in hair disorders. RESULTS:Standardized methods of assessing and tracking hair loss and growth, including new scoring techniques, response criteria, and end points in alopecia areata are presented. LIMITATIONS:The additional time to perform the assessments is the primary limitation to use of the methodology in clinical practice. CONCLUSION:Use of these measures will facilitate collection of standardized outcome data on therapeutic agents used in alopecia areata both in clinical practice and in clinical trials. 10.1016/j.jaad.2017.10.048
    Study on Serum Vitamin D in Alopecia Areata Patients. Marahatta Suchana,Agrawal Sudha,Khan Seraj Journal of Nepal Health Research Council BACKGROUND:Alopecia areata is the commonest cause of non-scarring alopecia. Few previous studies have found correlation between AA and vitamin D deficiency, suggesting that vitamin D deficiency can be a risk factor for Alopecia areata. To compare serum vitamin D level between Alopecia areata patients and healthy controls; and to assess the relation between serum vitamin D levels and AA disease severity. METHODS:This case control study included 30 newly diagnosed Alopecia areata patients. Thorough history was taken, detail examination was done and relevant findings were recorded in the standardized pro-forma. Their serum vitamin D (25-hydroxyvitamin D) levels were determined by competitive chemiluminescence methods; and were compared with that of age and sex matched healthy controls. Chi square test and Spearman's rho correlation test were used for the inferential statistics using SPSS version 11.5. RESULTS:There were 30 AA patients with mean age 28.37+10.07 years. Mean Severity of Alopecia Tool score was 3.56+3.50. Prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency was significantly higher in AA group (83.3%) compared to the control group (53.3%) (P=0.01). Similarly, serum 25(OH)D level was reduced more in Alopecia areata group (12.84, IQR=8.87-20.47) than the control group (29.5, IQR=19.85-41.27) (P=0.06). There was inverse co-relation between serum 25(OH)D level and SALT score. CONCLUSIONS:Prevalence of serum 25(OH)D deficiency was significantly higher in Alopecia areata group compared to the control, with inverse co-relation between its level and Alopecia areata disease severity. 10.33314/jnhrc.1475