RESUMO
Previous observational studies revealed controversy about the effect of circulating antioxidants on risk of alopecia. In the present study, we investigated the causal relationships between diet-derived circulating antioxidants and 2 non-scarring alopecia using Mendelian randomization (MR). Instrumental variables for antioxidants (lycopene, retinol, ascorbate, ß-carotene, α-tocopherol, and γ-tocopherol) were selected from published studies. Data for alopecia areata (AA) and androgenetic alopecia (AGA) was obtained from the FinnGen study project (R9 released in 2023), including 195 cases and 201,019 controls for AGA and 682 cases and 361,140 controls for AA. We used the inverse variance weighted method as the primary MR method. Three additional methods were used as sensitivity analysis to validate the robustness of the results. We found a causal relationship between absolute ß-carotene levels and AGA risk (Pâ =â .039), but not with AA (Pâ =â .283). The results of Wald ratio showed a protective effect of absolute ß-carotene levels against AGA, with per 0.1 ln-transformed ß-carotene being associated with a 76% lower risk of AGA (OR: 0.24, 95% CI: 0.06-0.93). Based on the fixed effects inverse variance weighting results, we found that α-tocopherol was protective against both AGA (Pâ =â .026) and AA (Pâ =â .018). For each unit increase in α-tocopherol, the effects of change in AGA and AA were 0.02 (95% CI: 0.00-0.61) and 0.10 (95% CI: 0.01-0.67), respectively. The results did not reveal any other causal relationships. Our study identified 3 causal associations of antioxidants with the risk of non-scarring alopecia. These results provide new insights into the prevention of non-scarring alopecia through diet.
Assuntos
Alopecia , Antioxidantes , Dieta , Análise da Randomização Mendeliana , beta Caroteno , Humanos , Antioxidantes/metabolismo , beta Caroteno/sangue , Alopecia/genética , Alopecia/sangue , alfa-Tocoferol/sangue , Feminino , Masculino , Alopecia em Áreas/sangue , Alopecia em Áreas/genética , Alopecia em Áreas/epidemiologia , Fatores de RiscoRESUMO
Alopecia areata (AA) is an autoimmune disease characterized by damage to hair follicles and hair loss. Cell-free DNA (cfDNA) has recently received attention as a biomarker of various disorders including inflammatory skin diseases. In this study, we aimed to investigate the clinical significance of cfDNA and the circulating DNAs of disease-associated cytokines in AA patients. Serum samples were obtained from 63 patients with AA and 32 healthy controls (HC). Using droplet digital polymerase chain reaction, circulating C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL11, C-X-C motif chemokine receptor 3, interferon (IFN)-γ, interleukin (IL) -7, IL-15, and Janus kinase (JAK) 2 were detectable in both HC and AA patients. Among the detectable DNAs, copies of circulating CXCL9, CXCL11, IL-15, IFN-γ, and JAK2 were significantly higher in AA patients than in HC. These results suggest that increased circulating DNA levels may reflect damage to hair follicles in AA patients.
Assuntos
Alopecia em Áreas , Ácidos Nucleicos Livres , Citocinas , Humanos , Alopecia em Áreas/sangue , Alopecia em Áreas/genética , Ácidos Nucleicos Livres/sangue , Masculino , Feminino , Adulto , Citocinas/sangue , Estudos de Casos e Controles , Biomarcadores/sangue , Pessoa de Meia-Idade , Adulto Jovem , Janus Quinase 2/genética , Janus Quinase 2/sangue , Quimiocina CXCL9/sangue , Quimiocina CXCL9/genética , Quimiocina CXCL11/sangue , Quimiocina CXCL11/genética , Interferon gama/sangue , Folículo Piloso , Quimiocina CXCL10/sangue , Adolescente , Interleucina-15/sangue , Interleucina-15/genéticaRESUMO
BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression in diverse biological processes. They hold promise as therapeutic candidates for targeting human disease pathways, although our understanding of their gene regulatory mechanism remains incomplete. Alopecia areata (AA) is a prevalent inflammatory ailment distinguished by the infiltration of T cells targeting the anagen-stage hair follicles. The scarcity of effective remedies for AA may stem from limited understanding regarding its precise cellular mechanism. AIM: To investigate and examine the importance and role of the miR-200c-3p as a genetic indicator for AA, and its possible impact on disease progression. SUBJECTS AND METHODS: Case-control study included 65 patients with AA and 65 matched healthy controls. A real-time PCR technique was used to measure the expression of miR-200c-3p for both groups. Bioinformatic tools were used for prediction with genes and gene-gene interaction, and protein-protein interaction. RESULTS: The expression levels of miR-200c-3p were significantly higher in AA patients than in healthy controls. We predicted that miR-200c-3p plays a markable role in the development of AA by its effect on the EGFR tyrosine kinase inhibitor resistance pathway. CONCLUSION: We were able to identify the influence of miR-200c-3p on both PLCG1 and RPS6KP1 genes which in turn regulate the EGFR tyrosine kinases resistance pathway that displayed the most substantial increase in activity. Our outcomes shed light on the era of the potential theranostic role of this innovative miRNA in AA.
Assuntos
Alopecia em Áreas , MicroRNAs , Humanos , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/genética , Estudos de Casos e Controles , Receptores ErbB/genética , Marcadores Genéticos , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Alopecia areata (AA) is a common non-scarring hair loss condition driven by the collapse of immune privilege and oxidative stress. The role of ferroptosis, a type of cell death linked to oxidative stress, in AA is yet to be explored, even though it's implicated in various diseases. Using transcriptome data from AA patients and controls from datasets GSE68801 and GSE80342, we aimed to identify AA diagnostic marker genes linked to ferroptosis. We employed Single-sample gene set enrichment analysis (ssGSEA) for immune cell infiltration evaluation. Correlations between ferroptosis-related differentially expressed genes (FRDEGs) and immune cells/functions were identified using Spearman analysis. Feature selection was done through Support vector machine-recursive feature elimination (SVM-RFE) and LASSO regression models. Validation was performed using the GSE80342 dataset, followed by hierarchical internal validation. We also constructed a nomogram to assess the predictive ability of FRDEGs in AA. Furthermore, the expression and distribution of these molecules were confirmed through immunofluorescence. Four genes, namely SLC40A1, LCN2, CREB5, and SLC7A11, were identified as markers for AA. A prediction model based on these genes showed high accuracy (AUC = 0.9052). Immunofluorescence revealed reduced expression of these molecules in AA patients compared to normal controls (NC), with SLC40A1 and CREB5 showing significant differences. Notably, they were primarily localized to the outer root sheath and in proximity to the sebaceous glands. Our study identified several ferroptosis-related genes associated with AA. These findings, emerging from the integration of immune cell infiltration analysis and machine learning, contribute to the evolving understanding of diagnostic and therapeutic strategies in AA. Importantly, this research lays a solid foundation for subsequent studies exploring the intricate relationship between AA and ferroptosis.
Assuntos
Alopecia em Áreas , Ferroptose , Humanos , Alopecia em Áreas/genética , Sistema y+ de Transporte de Aminoácidos/genética , Proteína A de Ligação a Elemento de Resposta do AMP Cíclico , Ferroptose/genética , Lipocalina-2 , Aprendizado de Máquina , Marcadores GenéticosRESUMO
Background: Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear. Objectives: This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata. Methods: genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks. Result: Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, p = 3.03×10-3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3. Conclusion: This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.
Assuntos
Alopecia em Áreas , Hipotireoidismo , Humanos , Alopecia em Áreas/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hipotireoidismo/complicações , Hipotireoidismo/genéticaRESUMO
BACKGROUND: Alopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. Although there is an increased understanding of AA pathogenesis and progress in its treatments, the outcome of AA patients remains unfavorable, especially when they are progressing to the subtypes of alopecia totalis (AT) or alopecia universalis (AU). Thus, identifying biomarkers that reflect the risk of AA progressing to AT or AU could lead to better interventions for AA patients. METHODS: In this study, we conducted bioinformatics analyses to select key genes that correlated to AU or AT based on the whole-genome gene expression of 122 human scalp skin biopsy specimens obtained from NCBI-GEO GSE68801. Then, we built a biomarker using 8 different machine learning (ML) algorithms based on the key genes selected by bioinformatics analyses. RESULTS: We identified 4 key genes that significantly increased (CD28) or decreased (HOXC13, KRTAP1-3, and GPRC5D) in AA tissues, especially in the subtypes of AT and AU. Besides, the predictive accuracy (area under the curve [AUC] value) of the prediction models for forecasting AA patients progressing to AT/AU models reached 90.7% (87.9%) by logistic regression, 93.8% (79.9%) by classification trees, 100.0% (76.3%) by random forest, 96.9% (76.3%) by support vector machine, 83.5% (79.9%) by K-nearest neighbors, 97.1% (87.3%) by XGBoost, and 93.3% (80.6%) by neural network algorithms for the training (internal validation) cohort. Besides, 2 molecule drugs, azacitidine and anisomycin, were identified by Cmap database. They might have the potential therapeutic effects on AA patients with high risk of progressing to AT/AU. CONCLUSIONS: In the present study, we conducted high accuracy models for predicting the risk of AA patients progressing to AT or AU, which may be important in facilitating personalized therapeutic strategies and clinical management for different AA patients.
Assuntos
Alopecia em Áreas , Alopecia/genética , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/genética , Biomarcadores , Biologia Computacional , Humanos , Aprendizado de MáquinaRESUMO
BACKGROUND: Alopecia areata (AA) is an autoimmune disease where autoimmune dysregulations along with genetic susceptibility are hypothesized to play a role in pathogenesis. OBJECTIVE: The aim of this study in to evaluate HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 profile and its relationship with clinical features in AA patients. MATERIALS AND METHODS: Ninety-eight patients with AA and 100 healthy controls were included in the study. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed using polymerase chain reaction-sequence specific primers (PCR-SSP). RESULTS: HLA-B*39 and HLA-HLA-DRB1*15 allele frequencies were increased (p = .022 and p = .023, respectively), HLA-A*11 and HLA-B*35 frequencies were decreased (p = .006 and p = .014, respectively) in AA patients. HLA-B*13 and HLA-DRB1*11 were associated with poor prognostic factors. A class I allele, HLA-B*13 was associated with recurrence (p = .023) and presence of nevus flammeus (p = .022), while the class II allele HLA-DRB1*11 was associated with widespread hair loss (diffuse or universal alopecia) (p = .026), presence of ophiasis (p = .049) and juvenile onset (p = .018). CONCLUSION: Belonging to two different classes of HLA family, HLA-B*13 and HLA-DRB1*11 alleles identified separate set of risk factors. In addition to increasing the risk of AA, HLA alleles may affect the prognosis of the disease.
Assuntos
Alopecia em Áreas , Alelos , Alopecia em Áreas/genética , Estudos de Casos e Controles , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , HumanosRESUMO
Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-ß) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy.
Assuntos
Alopecia em Áreas/sangue , Citocinas/sangue , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Alopecia em Áreas/genética , Alopecia em Áreas/imunologia , Alopecia em Áreas/patologia , Citocinas/classificação , Citocinas/genética , Humanos , Interleucina-12/sangue , Interleucina-17/sangue , Interleucina-2/sangue , Células Th1/patologia , Células Th17/patologia , Células Th2/patologia , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To explore the genetic basis for a patient with clinically suspected neurofibromatosis type I, alopecia areata and vitiligo. METHODS: Variant of the NF1 gene was detected by chip capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the family trio. RESULTS: The patient was found to harbor a novel missense c.1885G>A (p.Gly629Arg) variant of the NF1 gene, for which neither parent was carrier. The variant was not recorded in the public database. Based on the guidelines for genetic variation of the American College of Medical Genetics and Genomics, the c.1885G>A missense variant was predicted to be pathogenic (PS1+PS2+PM2+PP3+PP4). CONCLUSION: The c.1885G>A missense variant probably underlay the disease in this child. Above finding has enriched the spectrum of the NF1 gene variants.
Assuntos
Alopecia em Áreas , Neurofibromatose 1 , Vitiligo , Alopecia em Áreas/genética , Criança , Genômica , Humanos , Mutação , Neurofibromatose 1/genética , Vitiligo/genéticaRESUMO
OBJECTIVES: Genetic association studies on alopecia areata (AA) performed in various populations have shown heterogeneous results. The aim of the current review was to synthesize the results of said studies to estimate the impact of FAS, FASL, PTPN22, CTLA4 and IL2RA gene polymorphisms on AA susceptibility. DESIGN: A systematic literature search was conducted in the Medline, Web of Science, Scopus, EMBASE and LILACS databases. Studies published up to June 2020 were included. The results available in the grey literature including the Open Grey and Google Scholar databases were also used. The texts of potentially related studies were screened by individual reviewers. Evidence of publication bias was assessed using the Newcastle-Ottawa scale and the quality of evidence was assessed using the GRADE system. The quantitative synthesis was performed using the fixed effect model. RESULTS: Out of 1784 articles, we identified 18 relevant articles for the qualitative synthesis and 16 for the quantitative synthesis. In a study of rs2476601 polymorphism of PTPN22 gene, including 1292 cases and 1832 controls, a correlation was found with the risk of developing AA in the allelic model (OR1.49 [95% C:1.13-1.95]), the heterozygous codominant (OR1.44 [95% CI:1:19-1.76]) and dominant model (OR1.43 [95% CI:1.18-1.73]). No association was found between the presence of FASL, PTPN22, CTLA and IL2RA gene polymorphisms with AA susceptibility. CONCLUSIONS: The results suggest that the T allele of the single nucleoid polymorphism (SNP) rs2476601 in PTPN22 gene is a risk factor for developing alopecia areata. However, more robust studies defining the ethnic background of the population of origin are required, so that the risk identified in the present study can be validated. Additionally, a greater number of studies is necessary to evaluate the role of the FAS, FASL, PTPN22, CTLA4 and IL2RA genetic variants, given the heterogenous results found in the literature.
Assuntos
Alopecia em Áreas/genética , Antígeno CTLA-4/genética , Proteína Ligante Fas/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Receptor fas/genética , Alelos , Alopecia em Áreas/epidemiologia , Alopecia em Áreas/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Alopecia areata is an autoimmune hair loss disease with infiltration of pro-inflammatory cells into hair follicles. The role of Tgr5 in dermatitis has attracted considerable attention. The present study aimed to investigate the effect of Tgr5 in the development of Alopecia areata. METHODS: The study utilized a comparison control group design with four groups of wild-type group, wild-type+INT777 group, Tgr5-/- group, and Tgr5-/-+INT777 group. The mice were treated with INT777 (30 mg/kg/day) or the carrier solution (DMSO) intraperitoneally for 7 weeks, and the back skin was collected and analyzed by histology and immunohistochemistry staining. The lumbar vertebrae 4 has also been analyzed by DXA and Micro-CT. RESULTS: Tgr5-/- mice displayed the decreasingly significant in hair area and length, skin thickness, and the ratio of anagen and telogen, collagen, and mast cell number and loss the bone mass than WT group. After treating with INT777, the appearance of alopecia areata and bone microstructure has improved. Immunohistochemistry and qPCR analysis showed that activation of Tgr5 can down-regulate the express of JAK1, STAT3, IL-6, TNF-α, and VEGF. CONCLUSION: These findings indicate that activation of Tgr5 mediated amelioration of alopecia areata and osteoporosis by down-regulated JAK1-STAT3 signaling pathway.
Assuntos
Alopecia em Áreas/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Densidade Óssea/efeitos dos fármacos , Ácidos Cólicos/farmacologia , Folículo Piloso/efeitos dos fármacos , Vértebras Lombares/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Receptores Acoplados a Proteínas G/agonistas , Alopecia em Áreas/genética , Alopecia em Áreas/metabolismo , Alopecia em Áreas/fisiopatologia , Animais , Modelos Animais de Doenças , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Janus Quinase 1/genética , Janus Quinase 1/metabolismo , Vértebras Lombares/metabolismo , Vértebras Lombares/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The frequent coexistence of obesity and metabolic syndrome in patients with alopecia areata may indicate the common pathogenetic pathway in these conditions with an important role of adipokines. The aim of the study was to evaluate the serum level of adiponectin, resistin and leptin in patients with alopecia areata in comparison to healthy controls. The study included 65 patients with alopecia areata and 71 healthy controls. The concentration of adipokines was determined with the enzyme-linked immunosorbent assay. The mean concentrations of adiponectin and resistin were significantly lower in the sera of patients with alopecia areata when compared to healthy controls (7966 [Formula: see text] 4087 vs 9947 [Formula: see text] 5692 ng/ml; p = 0.0312 and 11.04 [Formula: see text] 3.88 vs 14.11 [Formula: see text] 8.69 ng/ml; p = 0.0176, respectively). A negative correlation between the serum level of adiponectin and severity of alopecia tool (SALT) score was observed (r = - 0.26; p < 0.05). The concentration of adiponectin was significantly lower in patients with alopecia universalis than in patients with patchy alopecia areata (4951 [Formula: see text] 2499 vs 8525 [Formula: see text] 4085 ng/ml; p = 0.0135). No significant difference in the serum concentration of leptin was observed between patients with alopecia areata and healthy controls. The negative correlation between the serum level of adiponectin and hair loss severity indicates that adiponectin may be considered a marker of hair loss severity in alopecia areata. Further studies are needed to evaluate the role of resistin in patients with alopecia areata and its decreased level irregardless of severity or activity of the disease.
Assuntos
Adiponectina/sangue , Alopecia em Áreas/sangue , Biomarcadores/sangue , Adiponectina/genética , Adulto , Alopecia em Áreas/genética , Alopecia em Áreas/patologia , Feminino , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Resistina/sangue , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Alopecia areata is a common non-scarring hair loss disorder. It has been generally recognised as a loss of immune privilege leading to an autoimmune attack upon anagen hair follicles. Survivin is one of the apoptosis inhibitor proteins, responsible for apoptosis suppression and cell cycle regulation. Survivin expression has been demonstrated in the matrix and outer root sheath keratinocytes of anagen hair follicles. Survivin overexpression was shown in several autoimmune diseases, and it was postulated that it contributes to the survival of self-reactive T and B cells. P53 is a tumour suppressor gene that was suggested to repress autoimmunity via induction of T regulatory cells. Survivin gene expression is transcriptionally suppressed by wild-type p53. AIM: The aim of this study was to investigate survivin and p53 genes expression in alopecia areata patients. METHODS: The mRNA tissue expression of survivin and p53 was measured by quantitative real-time polymerase chain reaction in lesional and non-lesional punch scalp biopsies of 25 alopecia areata patients and 25 healthy subjects. RESULTS: The study showed higher mRNA expression of survivin in lesional biopsies compared to non-lesional (P < 0.001) and control biopsies (P = 0.001). In non-lesional biopsies, the expression was significantly lower than in control biopsies (P < 0.001). The expression of p53 was lower in both lesional and non-lesional biopsies relative to control biopsies. However, the difference was only significant in non-lesional biopsies (P = 0.017). CONCLUSION: Our results suggested that survivin and p53 genes expression was altered in patients with alopecia areata.
Assuntos
Alopecia em Áreas/genética , Genes p53 , Survivina/metabolismo , Adolescente , Adulto , Biópsia por Agulha , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Couro Cabeludo/metabolismo , Couro Cabeludo/patologia , Survivina/genética , Adulto JovemRESUMO
PURPOSE & METHODS: Several single-nucleotide polymorphisms (SNPs) in the promoter region of the TNF-α gene can cause variations in the gene regulatory sites and act as risk factors for some autoimmune disorders as alopecia areata (AA) and vitiligo. This study aimed to detect the serum TNF-α (sTNF) level (by ELISA) and the rs1800629 (by real-time PCR) among AA and vitiligo Egyptian patients and to determine their relation with disease duration and severity. In silico analysis of this SNP to study the molecular regulation of the mutant genotypes was also done. RESULTS: In AA patients, no risk was associated with the mutant genotypes vs. the normal genotype, or with A allele vs. G allele. The risk of vitiligo was significantly higher with the G/A and A/A genotypes compared with HCs (p = 0.011). Similarly, a significantly increased risk was noted in patients with A allele vs. G allele (p<0.0001). In AA and vitiligo patients, a significant increase in sTNF-α levels was noted in the mutant G/A genotypes vs. the normal G/G genotype (p<0.0001) and in the A allele vs the G allele (p<0.0001). According to the in silico analysis, this SNP could mainly affect the SP1 transcription factor binding site with subsequent effect on TNF-α expression. CONCLUSION: According to results of the laboratory and the in silico study, the mutant TNF-α (308) genotypes were risk factors that conferred susceptibility to vitiligo among Egyptian patients but had no effect on the susceptibility to AA.
Assuntos
Alopecia em Áreas/genética , Modelos Genéticos , Fator de Necrose Tumoral alfa/genética , Vitiligo/genética , Adolescente , Adulto , Alopecia em Áreas/diagnóstico , Estudos de Casos e Controles , Criança , Pré-Escolar , Simulação por Computador , Egito , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Fatores de Risco , Índice de Gravidade de Doença , Vitiligo/diagnóstico , Adulto JovemRESUMO
La alopecia areata es un tipo común de alopecia no cicatricial. Aunque la patogénesis exacta permanece sin dilucidar, se piensa que la alopecia areata tiene una etiología multifactorial en donde se interrelacionan predisposición genética y factores ambientales. En pacientes susceptibles, se han documentado que el estrés, infecciones y microtraumas disminuyen las citoquinas inmunosupresoras que normalmente mantienen el privilegio inmune del folículo piloso. Actualmente no hay terapia curativa para la alopecia areata, aunque ciertos tratamientos pueden inducir el crecimiento del cabello en un porcentaje de pacientes. Se postula que la simvastatina restablece el privilegio inmune y ezetimibe aportaría un efecto inmunomodulador y antiinflamatorio. Se presenta el caso de una mujer de 23 años con alopecia areata, exitosamente tratada con simvastatina y ezetimibe.
Alopecia areata is a common type of non-scarring alo¬pecia. Although the exact pathogenesis remains elusive, alopecia areata is thought to have a multifactorial etiology described as an interplay of genetic predisposition and environmental exposures. In patients with genetic susceptibility, stress, infection, and microtrauma have been documented to decrease immunosuppressive cytokines that generally maintain the hair follicle's immune privilege. There is currently no curative therapy for alopecia areata, although some treatments can induce hair growth in a percentage of patients. It has been postulated that simvastatin reestablishes the immune privilege, and ezetimibe would provide an immunomodulatory and anti-inflammatory effect. We report a case of a 23 years-old woman with alopecia areata successfully treated with simvastatin/ezetimibe.
Assuntos
Humanos , Feminino , Adulto , Adulto Jovem , Sinvastatina/uso terapêutico , Alopecia em Áreas/genética , Alopecia em Áreas/tratamento farmacológico , Ezetimiba/uso terapêutico , Imunossupressores/uso terapêutico , Predisposição Genética para DoençaRESUMO
Alopecia areata (AA) and vitiligo are both common skin diseases of autoimmune origin. Both alopecia areata and vitiligo have shown to be affected by oxidative stress. The present work is aimed at evaluating and comparing the serum proinflammatory cytokine levels in AA and nonsegmental vitiligo (NSV). A cross-sectional study was conducted of 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of interferon γ (IFN-γ), interleukin- (IL-) 1ß, and IL-6 were determined quantitatively by ELISA method. Our analysis identified a signature of oxidative stress associated with AA and NSV, characterized by elevated levels of IFN-γ (AA: p = 0.007283; NSV: p = 0.038467), IL-1ß (AA; NSV: p ≤ 0.001), and IL-6 (AA; NSV: p ≤ 0.001). IL-6 was also significantly increased in NSV patients in comparison with AA patients (p = 0.004485). Our results supported the hypothesis that oxidative stress may play a significant role in promoting and amplifying the inflammatory process both in AA and vitiligo. The complex understanding of both disease etiopathogenesis involves interrelationships between oxidative stress and autoimmunity. The clinical study registration number is RNN/266/16/KE.
Assuntos
Alopecia em Áreas/genética , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Vitiligo/genética , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Abstract Background: Alopecia areata is an autoimmune disease that produces non-scarring hair loss around the body. Gene variants of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a negative regulator of T-cell response, have been associated with a predisposition to autoimmune diseases in different populations; however, the involvement of these genetic variants in the development of AA is controversial. Objective: The present study evaluated the potential association of two CTLA4 gene variants with alopecia areata in a Mexican population. Methods: We genotyped +49AG (rs231775) and CT60 (rs3087243) variants in 50 AA patients and 100 healthy control participants through PCR-RFLP. Results: No statistical difference was observed for either of the gene variants regarding allele or genotype frequencies between AA patients and the controls when the parameters of family/personal history of autoimmune diseases or gender were considered (p > 0.05). Study limitations: Small sample size of patients and the data were obtained from Northeast Mexico population. Conclusion: The genetic variants rs231775 and rs3087243 of the CTLA4 gene are not a risk factor for the development of alopecia areata in the analyzed Mexican population.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Variação Genética/genética , Alopecia em Áreas/genética , Antígeno CTLA-4/genética , Estudos de Casos e Controles , Fatores de Risco , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Estudos de Associação Genética , Técnicas de Genotipagem , Frequência do Gene , México , Pessoa de Meia-IdadeRESUMO
Alopecia areata (AA) is a common alopecia characterized by non-scarring hair loss with the dysregulated immunity. However, the pathogenesis of AA remains to be elucidated. In this study, we identified gene signatures and then analyzed transcription factor-immune regulatory network in AA using integrated bioinformatics methods. Finally, we verified potential target genes in lesions of AA patients using qPCR and immunohistochemistry. Here, 74 differentially expressed genes (DEGs) were identified in AA, which were enriched in immune-related signaling pathway. The immune analysis revealed the infiltration of γδT cells and Macrophages M1 in AA lesion. Next, the expression correlation analysis and ChIP-seq results revealed a transcription factor (EOMEs) regulated network. We found that EOMEs, a T-box transcription factor, may be involved in the immunoregulation in AA via targeting CD8A and BMP2, and it may affect keratinocytes function via regulating GZMK, LYPD6, RNF182, KRTAP5-9 and KRT73 expression. Finally, the mRNA expression of these network genes in AA lesions was confirmed using qPCR. And the increase expression of EOMEs was identified at inflammatory cells at the periphery of hair follicles and partial keratinocytes in AA tissue using immunohistochemistry. In conclusions, our research demonstrated that EOMEs may play a key role in the progression of AA via regulating immune cell infiltration and keratinocytes function, indicating EOMEs as a promising therapeutic target of AA.
Assuntos
Alopecia em Áreas/genética , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Adolescente , Adulto , Progressão da Doença , Feminino , Folículo Piloso/imunologia , Humanos , Linfócitos Intraepiteliais/imunologia , Queratinócitos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Mapas de Interação de Proteínas , Transcriptoma , Adulto JovemRESUMO
BACKGROUND: Alopecia areata (AA) has long been associated with major depressive disorder (MDD). However, most evidence to date has derived from cross-sectional or case-control studies. OBJECTIVE: To investigate the bidirectional association between AA and MDD among probands and unaffected siblings. METHODS: Study participants were recruited from the National Health Insurance Research Database in Taiwan. We included 2123 probands with AA, 2298 unaffected siblings, and 9192 matched controls to assess the risk of MDD. We included 16,543 probands with MDD, 17,352 unaffected siblings, and 69,408 matched controls to assess the risk of AA. The Breslow-Cox model was used to calculate the adjusted relative risk. RESULTS: Compared with controls, AA probands and unaffected siblings had adjusted relative risks of 8.22 (95% confidence interval [CI], 6.41-10.54) and 2.55 (95% CI, 1.91-3.40), respectively, for MDD. MDD probands and unaffected siblings had adjusted relative risks for AA of 1.66 (95% CI, 1.24-2.22) and 1.64 (95% CI, 1.27-2.12), respectively. LIMITATION: The National Health Insurance Research Database lacked information on disease severity, body mass index, smoking habit, alcohol consumption, and stressful life events. CONCLUSION: Our study demonstrated a bidirectional association between AA and MDD among probands and unaffected siblings, thus suggesting shared familial mechanisms underlying AA and MDD.