RESUMO
OBJECTIVE: Cellular and humoral immunity plays a role in the pathogenesis of vitiligo. T lymphocytes and natural killer cells involved in cellular immunity carry out their cytotoxic activities through perforin/granzyme-dependent granule exocytosis, in which granulysin and cathepsin-L are also involved. The aim of this study was to investigate the possible role of serum granulysin and cathepsin-L in the etiopathogenesis of vitiligo and their association with disease activity and severity. METHODS: This randomized, prospective case-control study was conducted with 46 vitiligo patients admitted to the hospital for vitiligo between January and November 2021 and 46 healthy volunteers of similar age and gender. Serum levels of granulysin and cathepsin-L were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean serum levels of granulysin and cathepsin-L were statistically significantly higher in vitiligo patients compared with the control group (p=0.048 and p=0.024, respectively). There was no statistically significant correlation between serum granulysin and serum cathepsin-L levels and disease severity in the patient group (r=0.30, p=0.062 and r=0.268, p=0.071, respectively). Disease activity also showed no significant association with serum granulysin and cathepsin-L levels (p=0.986 and p=0.962, respectively). CONCLUSION: Although granulysin and cathepsin-L are molecules involved in the pathogenesis of vitiligo, the use of these molecules may not be helpful in assessing disease activity and severity. It may be helpful to conduct comprehensive and prospective studies to find new molecules to fill the gap in this area.
Assuntos
Antígenos de Diferenciação de Linfócitos T , Catepsina L , Índice de Gravidade de Doença , Vitiligo , Humanos , Vitiligo/sangue , Feminino , Masculino , Antígenos de Diferenciação de Linfócitos T/sangue , Adulto , Estudos de Casos e Controles , Estudos Prospectivos , Adulto Jovem , Pessoa de Meia-Idade , Catepsina L/sangue , Ensaio de Imunoadsorção Enzimática , Adolescente , Biomarcadores/sangueAssuntos
Quimiocina CXCL10/sangue , Interleucina-18/sangue , Terapia Ultravioleta/métodos , Vitiligo/radioterapia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pigmentação da Pele/efeitos da radiação , Resultado do Tratamento , Vitiligo/sangue , Vitiligo/diagnóstico , Adulto JovemRESUMO
BACKGROUND: The macrophage migration inhibiting factor (MIF) is a protein that promotes the activation of immune cells and the production of other proinflammatory cytokines such as TNF-α, IL-1ß, and IFN-γ, which have proposed to play an essential role in the pathogenesis of vitiligo. The study aimed to assess the association between MIF polymorphisms (-794 CATT5-8 and -173 G>C), MIF in situ expression, and MIF serum concentrations with susceptibility and disease activity in patients with non-segmental vitiligo (NSV) from western Mexico. METHODS: The study included 111 patients with NSV and 201 control subjects. Genotyping was performed by conventional PCR (-794 CATT5-8 ) and PCR-RFLP (-173 G>C) methods. MIF mRNA expression was quantified by real-time PCR and MIF serum concentrations were determined by ELISA kit. Histopathological samples were analyzed by automated immunohistochemistry. RESULTS: The MIF polymorphisms were associated with NSV susceptibility. Serum concentrations of MIF were higher in patients with active NSV and correlated negatively with the years of evolution. The depigmented skin from patients with active vitiligo showed a high expression of MIF. CONCLUSION: MIF polymorphisms increase the risk of NSV in the western Mexican population. The serum concentrations of MIF and in situ expression are associated with active NSV.
Assuntos
Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único , Vitiligo/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , México , Pessoa de Meia-Idade , Vitiligo/sangueRESUMO
BACKGROUND/OBJECTIVES: To investigate the association between vitiligo and metabolic syndrome. METHODS: A prospective cross-sectional study was conducted between 2014 and 2016. Study (n=155) and control groups (n=155) were evaluated for metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation criteria. Study group was divided into three groups according to their vitiligo area severity index and vitiligo disease activity score values (Group 1: 6.89 for VASI score, Group A: -1-0, Group B: 1-2 and Group C: 3-4 for vitiligo disease activity score respectively). MetS rates according to both criteria were compared between the vitiligo disease activity score and vitiligo area severity index groups. RESULTS: Metabolic syndrome rates were 37.4% and 40% in the study group and 19.4% and 26.5% in the control group according to National CholesterolEducation Program Adult Treatment Panel III and International Diabetes Federation criteria, respectively (p<001 and p=0.011). Metabolic syndrome was more frequent in vitiligo area severity index Groups 2 and 3 compared to vitiligo area severity index Group 1, and in vitiligo disease activity score Group C compared to vitiligo disease activity score Groups A and B. STUDY LIMITATIONS: Single center experience, absence of more specific oxidative-stress markers and lack of long-term follow-up of the patients. CONCLUSIONS: Frequency of metabolic syndrome was higher in patients with non-segmental vitiligo and the rate was higher in active/severe form of the disease.
Assuntos
Síndrome Metabólica/epidemiologia , Vitiligo/epidemiologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não Paramétricas , Turquia/epidemiologia , Deficiência de Vitamina B 12/sangue , Vitiligo/sangue , Vitiligo/complicações , Adulto JovemRESUMO
Abstract Background/Objectives: To investigate the association between vitiligo and metabolic syndrome. Methods: A prospective cross-sectional study was conducted between 2014 and 2016. Study (n = 155) and control groups (n = 155) were evaluated for metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation criteria. Study group was divided into three groups according to their vitiligo area severity index and vitiligo disease activity score values (Group 1: 6.89 for VASI score, Group A: −1-0, Group B: 1-2 and Group C: 3-4 for vitiligo disease activity score respectively). MetS rates according to both criteria were compared between the vitiligo disease activity score and vitiligo area severity index groups. Results: Metabolic syndrome rates were 37.4% and 40% in the study group and 19.4% and 26.5% in the control group according to National CholesterolEducation Program Adult Treatment Panel III and International Diabetes Federation criteria, respectively (p < 001 and p = 0.011). Metabolic syndrome was more frequent in vitiligo area severity index Groups 2 and 3 compared to vitiligo area severity index Group 1, and in vitiligo disease activity score Group C compared to vitiligo disease activity score Groups A and B. Study limitations: Single center experience, absence of more specific oxidative-stress markers and lack of long-term follow-up of the patients. Conclusions: Frequency of metabolic syndrome was higher in patients with non-segmental vitiligo and the rate was higher in active/severe form of the disease.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Adulto Jovem , Síndrome Metabólica/epidemiologia , Valores de Referência , Turquia/epidemiologia , Vitiligo/complicações , Vitiligo/sangue , Deficiência de Vitamina B 12/sangue , Índice de Gravidade de Doença , Incidência , Estudos Transversais , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Estatísticas não Paramétricas , Síndrome Metabólica/complicações , Síndrome Metabólica/sangue , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Vitiligo is a pigmentation disorder of autoimmune aetiology. Polymorphisms in beta-defensin genes have been linked to a predisposition to some autoimmune disorders. AIM: To evaluate the role of polymorphisms in DEFB1, the gene encoding for human beta-defensin (HBD)-1 and its 5' untranslated region in nonsegmental vitiligo. METHODS: In total, 354 participants [171 patients with non-segmental vitiligo and 183 age and sex-matched healthy controls (HCs)], were genotyped by the PCR-restriction fragment length polymorphism (RFLP) method. For 80 of these individuals (40 patients and -40 HCs) serum HBD-1 was also measured by ELISA. RESULTS: The -44 G allele, CG genotype and GGG haplotype increased the risk for vitiligo (P < 0.02 in all cases), whereas the -20 AA genotype seems to be protective (P = 0.04). Serum HBD-1 levels were lower in patients with vitiligo than in HCs (P < 0.01), as well as in patients with active vitiligo compared with those with stable vitiligo and with HCs (P < 0.05 in both cases), CONCLUSION: Our results suggest that HBD-1 and its gene polymorphisms may modulate vitiligo susceptibility and/or disease activity. This is the first report, to our knowledge, of the association of serum HBD-1 levels and DEFB1 gene polymorphisms with vitiligo.
Assuntos
Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único , Vitiligo/genética , beta-Defensinas/genética , Regiões 5' não Traduzidas , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , Índice de Gravidade de Doença , Vitiligo/sangue , Adulto Jovem , beta-Defensinas/sangueRESUMO
BACKGROUND: Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. OBJECTIVE: To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. METHODS: Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. RESULTS: There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. STUDY LIMITATIONS: Small number of investigated subjects. CONCLUSIONS: Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.
Assuntos
Fatores Inibidores da Migração de Macrófagos/análise , Fatores Inibidores da Migração de Macrófagos/fisiologia , RNA Mensageiro , Vitiligo/sangue , Vitiligo/etiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , ELISPOT , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Vitiligo/patologia , Adulto JovemRESUMO
Abstract: Background: Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. Objective: To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Methods: Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. Results: There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Study limitations: Small number of investigated subjects. Conclusions: Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Vitiligo/etiologia , Vitiligo/sangue , RNA Mensageiro , Fatores Inibidores da Migração de Macrófagos/análise , Fatores Inibidores da Migração de Macrófagos/fisiologia , Valores de Referência , Fatores de Tempo , Vitiligo/patologia , Índice de Gravidade de Doença , Estudos de Casos e Controles , Expressão Gênica , Estatísticas não Paramétricas , ELISPOT , Reação em Cadeia da Polimerase em Tempo RealRESUMO
We detected autoantibodies against melanocytes in serum samples obtained from 50 patients, including 4 with HBV, with vitiligo and identified the associated membrane antigens. Heat shock protein 70 (HSP70) and anti-tyrosinase-related protein 1 (TRP-1) antibody levels were analyzed. The associated antigens in normal human melanocyte were identified by immunofluorescence. Autoantibodies against melanocyte membrane and cytoplasmic proteins were detected by western blot. Membrane antigens with higher frequencies were identified by protein mass spectrometry. The HSP70 and anti-TRP-1 antibody levels (N = 70; 10 with HBV) were detected by ELISA. The specific antigens were detected in melanocyte cytoplasm and membrane (40/50; 80% incidence; western blot). The autoantibodies reacted with several membrane antigens with approximate molecular weights (Mr) of 86,000, 75,000, 60,000, 52,000, and 44,000 (strip positive rates: 36, 58, 22, 2, and 2%, respectively). Thirty percent of the patients showed the presence of cytoplasmic antigens (Mr: 110,000, 90,000, 75,000, 50,000, and 400,000; strip positive rates: 12, 4, 12, 10, and 2%, respectively). Fifteen and 5% of the healthy subjects showed positive expression of membrane and cytoplasmic antigens, respectively. Protein mass spectrometry predicted membrane proteins with Mr of 86,000 and 75,000 and 60,000 to be Lamin A /C and Vimentin X1, respective. High titers of anti-TRP-1 antibody were detected and showed positive correlation with HSP70 (r = 0. 927, P < 0. 01). This study identified a novel membrane antigen associated with vitiligo, which might assist future investigations into autoimmune pathogenesis of vitiligo and formation of autoantibodies. HBV infection was correlated to vitiligo.