RESUMEN
We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4 percent) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3 percent were male and follow-up range was 8.5 to 16 years. Two cases (13.3 percent) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3 percent) presented MRI with multiple large lesions. CSF was normal in 73.3 percent. The severe disability observed at EDSS onset improved in 86.66 percent patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.
Avaliamos as frequencia, características demográficas, clínicas e de associação genética dos alelos HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 e DPA1*0301 em pacientes com diagnóstico de encefalomielite aguda disseminada (ADEM) em população com doença desmielinizante do SNC. Quinze (8,4 por cento) pacientes de nossa série foram diagnosticados como ADEM. A média de idade foi 35,23 anos (variando entre 12 e 77), 53,3 por cento eram homens e o tempo de acompanhamento variou entre 8,5 e 16 anos. Dois casos (13,3 por cento) apresentaram infecção prévia, um apresentou processo desmielinizante para infeccioso e outro havia se submetido a vacinação para hepatite B quatro semanas antes. O EDSS variou entre 3,0 e 9,5. Oito pacientes (53,3 por cento) apresentaram grandes lesões na RM. O LCR foi normal em 73,3 por cento. A incapacidade grave quantificada pelo EDSS foi seguida de melhora importante em 86,6 por cento dos pacientes. A susceptibilidade genética na ADEM foi significativamente associada com os alelos HLA DQB1*0602, DRB1*1501 e DRB1*1503 (p<0,05) nos pacientes com quadro monofásico.
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Encefalomielitis Aguda Diseminada/genética , Frecuencia de los Genes/genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Estudios de Casos y Controles , Encefalomielitis Aguda Diseminada/patología , Genotipo , Imagen por Resonancia Magnética , Reacción en Cadena de la Polimerasa , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
Asunto(s)
Adolescente , Adulto , Anciano , Pueblo Asiatico/genética , Autoanticuerpos/genética , Femenino , Expresión Génica , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/etnología , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Lupus Eritematoso Sistémico/etnología , Malasia/etnología , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
The HLA-D region of the major histocompatibility complex has several subregions, the most important of which are DR, DQ and DP. The genes coding for the beta chains of these proteins present most of the polymorphisms which result in the large variety of class II antigens observed. We have studied the restriction fragment length polymorphism (RFLP) of the DQ beta and DP beta genes in order to establish accurate typing patterns. The data show that DQ typing based on RFLP permits the identification of the recently described DQw1 splits (new antigenic specificities), DQw5 and DQw6. The TA 10-monoclonal antibody-positive split of DQw3, designated DQw7, is associated with specific DNA fragments after digestion with four different enzymes: Taq I, Hind III, Pvu II and Bg1 II. Furthermore, the recently reported specificity DQw4 (formerly typed as a blank) is associated with a specific 2.4-kb fragment when the DNA is digested with EcoRV. DP typing proved to be more difficult even though six enzymes were used, and only broad groups could be identified