RESUMO
Abstract The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Labiais/imunologia , Antígenos HLA-DR/imunologia , Queilite/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Neoplasias Labiais/patologia , Neoplasias Labiais/secundário , Queilite/patologia , Gradação de Tumores , Carcinogênese/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Inflamação/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Introducción. Las espondiloartritis son enfermedades reumatológicas crónicas que afectan el esqueleto axial y las articulaciones periféricas, con varias manifestaciones extraarticulares. La asociación con el HLA-B27 sigue siendo uno de los vínculos más fuertes conocidos entre estas entidades y el complejo mayor de histocompatibilidad; sin embargo, la distribución mundial del HLA-B27 varía considerablemente y se han descrito asociaciones con genes no HLA-B27. Objetivo. Conocer la frecuencia de alelos HLA de clase I y II en pacientes con espondiloartritis provenientes del noroccidente colombiano y su frecuencia en las manifestaciones clínicas y radiológicas específicas. Materiales y métodos. Se condujo un estudio descriptivo, observacional, de corte transversal, retrospectivo y prospectivo entre 2005 y 2008 de 56 pacientes colombianos con espondiloartritis. Se identificaron los alelos correspondientes a los loci HLA de clase I y II (HLA-B, HLADQB1 y HLADRB). Se analizó su frecuencia con las manifestaciones clínicas axiales, periféricas, extraarticulares y radiológicas. Resultados. Se encontró una baja frecuencia de HLA-B27 en la población total (50 %), aunque fue el alelo más frecuente, junto con HLA-DRB4*01 (35,7 %) y HLA-DQB1*0501 (28,6 %), en todos los pacientes en general y en cada una de las manifestaciones clínicas y radiológicas. Se resalta la alta frecuencia de HLA-B27 y HLA-DRB4*01 (64,3 %) en pacientes con dactilitis, hallazgo novedoso sin previa descripción. Conclusión. Los alelos HLA-B27, HLA-DRB4*01 y HLA-DQB1*0501 fueron frecuentes en los diferentes subtipos de espondiloartritis y en las manifestaciones clínicas axiales, periféricas y extraarticulares específicas, además de la sacroiliítis radiológica.
Introduction. Spondyloarthritis is a chronic rheumatic disease that affect the axial skeleton and peripheral joints, along with several extra-articular manifestations. The association with HLA-B27 remains one of the strongest known links between these entities and the major histocompatibility complex. However, the global distribution of HLA-B27 varies considerably and furthermore, associations with non-HLA-B27 genes have been described. Objective. The frequency of HLA class I and II was determined in a population of patients with spondyloarthritis with respect to detection in the clinical setting and by radiology. Materials and methods. A descriptive, observational, cross-sectional, retrospective and prospective study was conducted in 56 patients from northwestern Colombia. Each was diagnosed with spondyloarthritis between 2005 and 2008. In each case, alleles were identified for the loci HLA class I and II (HLA-B; HLADQB1 and HLADRB). The frequency of these alleles in the axial, peripheral, extraarticular and radiological manifestations. Results.The frequency of HLA-B27 was 50% overall, and it was the most frequent allele. The two other alleles were HLA.DRB4*01 at 35.7% and HLA-DQB1*0501 at 28.6%, as detected in each of the clinical and radiological manifestations. A high frequency of HLA-B27 and HLA-DRB4*01 (64.3%) was noted in patients with dactylitis. Conclusion. The alleles HLA-B27, HLA-DRB4*01 and HLA-DQB1*0501 were common in the different subtypes of spondyloarthritis and were frequent in the specific clinical axial, peripheral and extraarticular clinical manifestations, as well as radiological sacroiliitis.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Genes MHC Classe I , Genes MHC da Classe II , Espondilartrite/genética , Alelos , Estudos de Coortes , Comorbidade , Estudos Transversais , Colômbia/epidemiologia , Enterite/epidemiologia , Enterite/genética , Frequência do Gene , Predisposição Genética para Doença , /genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , /genética , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sequência de DNA , Sacroileíte/epidemiologia , Sacroileíte/genética , Sacroileíte , Espondilartrite/epidemiologia , Espondilartrite , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/genética , Espondilite Anquilosante , Uveíte/epidemiologia , Uveíte/genéticaRESUMO
Vogt-Koyanagi-Harada disease (VKH), a well-established multiorgan disorder affecting pigmented structures, is an autoimmune disorder of melanocyte proteins in genetically susceptible individuals. Several clinical and experimental data point to the importance of the effector role of CD4+ T cells and Th1 cytokines, the relevance of searching a target protein in the melanocyte, and the relevance of the HLA-DRB1*0405 in the pathogenesis of the disease. Vogt-Koyanagi-Harada disease has a benign course when early diagnosed and adequatey treated. Full-blown recurrences are rare after the acute stage of Vogt-Koyanagi-Harada disease is over. On the other hand, clinical findings, such as progressive tissue depigmentation (including sunset glow fundus) and uveitis recurrence, indicate that ocular inflammation may persist after the acute phase. Additionally, indocyanine green angiography findings suggest the presence of choroidal inflammation in eyes without clinically detectable inflammation. The aim of this paper is to review the latest research results on Vogt-Koyanagi-Harada disease pathogenesis and chronic/convalescent stages, which may help to better understand this potentially blinding disease and to improve its treatment.
A doença de Vogt-Koyanagi-Harada (VKH) afeta vários órgãos que têm em comum a presença de pigmento. É doença autoimune que agride os melanócitos de indivíduos geneticamente susceptíveis. Inúmeras evidências clínicas e experimentais demonstram a importância de células T CD4+ como células efetoras da resposta imune celular, das citocinas pró-inflamatórias Th1, da procura da proteína-alvo dentro do melanócito, e da relevância do HLA-classe II DRB1*0405 na patogênese desta doença. A doença de Vogt-Koyanagi-Harada apresenta bom prognóstico visual desde que o diagnóstico seja precoce e o tratamento instituído seja adequado. Recidivas com acometimento do segmento posterior são raras após a fase aguda da doença. No entanto, achados clínicos como a progressiva despigmentação do fundo, incluindo o aspecto em por do sol, e as recidivas da uveíte indicam que a inflamação ocular pode persistir mesmo após a fase aguda da doença. Os achados da angiografia com indocianina verde também sugerem a presença de inflamação da coróide mesmo em olhos sem inflamação clinicamente detectável. O objetivo do presente trabalho é rever os mais recentes estudos sobre a patogênese da doença Vogt-Koyanagi-Harada e sobre os aspectos clínicos da fase crônica e/ou convalescente da doença, permitindo melhores conhecimentos sobre esta doença potencialmente mórbida e oferecendo terapias mais adequadas.
Assuntos
Humanos , Síndrome Uveomeningoencefálica , Doença Crônica , Antígenos HLA-DR/imunologia , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/etiologiaRESUMO
A síndrome de Vogt-Koyanagi-Harada é doença crônica, sistêmica e auto-imune, com manifestações oculares, nervosas, auditivas e tegumentares. Descrevemos aqui o caso de uma criança com início dos sintomas aos quatro anos e dois meses de idade, com positividade para o HLA DRB1*01.
Vogt-Koyanagi-Harada syndrome is chronic systemic autoimmune disease with ocular, nervous, auditory and tegumental manifestations. We report here the case of a child with onset of symptoms at four years and two months of age, with positive HLA DRB1*01.