RESUMEN
Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55% of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1%) and HLA-DQB1*02 (52.9 vs 38.7%) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0%) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1%) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.
Asunto(s)
Antivirales/uso terapéutico , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Hepatitis C Crónica/genética , Interferón-alfa/uso terapéutico , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/inmunología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , Adulto JovenRESUMEN
Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55 percent of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1 percent) and HLA-DQB1*02 (52.9 vs 38.7 percent) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0 percent) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1 percent) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antivirales/uso terapéutico , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Hepatitis C Crónica/genética , Interferón-alfa/uso terapéutico , Estudios de Casos y Controles , Frecuencia de los Genes , Genotipo , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/inmunología , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , Adulto JovenRESUMEN
This study aimed to analyse the association of gene polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation. We studied 122 donor/recipient pairs who received HLA-identical transplants from siblings at the Universidade Estadual de Campinas, Brazil, between June 1996 and June 2006. Donor/recipient alleles for TNFA-238 and IL2-330/+166 single-nucleotide polymorphisms (SNP) were analysed by PCR-SSP. No association was observed between the risk of acute graft-versus-host disease (GVHD) and these SNP. However, our findings suggest that the polymorphism of promoter gene TNFA-238GA is associated with the occurrence and severity of chronic GVHD. The probability of chronic GVHD in patients with GA genotype at position -238 of TNFA gene is 91.7% in contrast to 59.4% in patients with GG genotype (P = 0.038). In patients with donor GA genotype the probability of chronic GVHD is 90.8%, and 57.9% in patients with donor GG genotype (P = 0.038). The probability of extensive chronic GVHD in patients with TNFA-238GA is 91.7% compared with 46.3% in patients with TNFA-238GG (P = 0.0046). In patients with donor GA genotype at position -238 of the TNFA gene, it is 81.7%, compared with 44.5% in patients with donor GG genotype (P = 0.016). However, further studies with more patients are required to identify cytokine gene polymorphisms and their association with transplant-related complication in Brazil, particularly due to ethnic background, the relatively low power of detection of genetic markers of this study, and the complexity of the MHC region.
Asunto(s)
Enfermedad Injerto contra Huésped/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Interleucina-2/genética , Polimorfismo Genético/genética , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Brasil , Niño , Femenino , Genotipo , Enfermedad Injerto contra Huésped/inmunología , Humanos , Lactante , Interleucina-2/inmunología , Leucemia/genética , Leucemia/terapia , Masculino , Persona de Mediana Edad , Polimorfismo Genético/inmunología , Hermanos , Donantes de Tejidos , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
AIM: The influence of panel-reactive antibody level (%PRA) on crossmatch results was evaluated among 866 patients on the waiting list for cadaveric renal allografting from January 2001 to August 2005. We evaluated the results for 124 potential donors for a kidney, including 2008 crossmatches. Four hundred eighteen patients were tested against only 1 donor. METHODS: Serum samples were screened for anti-HLA antibodies using immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) PRA kit and the %PRA of the most reactive sample (peak) was used for patient stratification, according to sensitization level. Crossmatches were performed on fresh donor T lymphocytes from peripheral lymph nodes, using classical and anti-human-globulin enhanced complement-dependent cytotoxicity (CDC-T) methods. The tests were performed using peak and current patient sera before and after dithiothreitol treatment. The crossmatch was assumed to be negative when no reactivity was observed in all tests. RESULTS: The incidences of positive crossmatch were as follows: 72.3%, 14.6%, and 7.2%, among patients with PRA >50%, PRA
Asunto(s)
Prueba de Histocompatibilidad/métodos , Isoanticuerpos/inmunología , Trasplante de Riñón/inmunología , Sistema del Grupo Sanguíneo ABO/inmunología , Cadáver , Rechazo de Injerto/inmunología , Humanos , Linfocitos T/inmunología , Donantes de Tejidos , Listas de EsperaRESUMEN
The application of DNA-based methods for human leukocyte antigen (HLA) genotyping has revealed an ever-increasing degree of polymorphism within the HLA-DRB loci and has resulted in the discovery of new alleles. We have identified a new DRB1 allele that was subsequently named DRB1*1360 by the WHO Nomenclature Committee. This allele is unusual for a DRB1*13 allele, as it is present on a DRB5 haplotype rather than the normal DRB3 haplotype found in association with DRB1*13 alleles.
Asunto(s)
Antígenos HLA-DR/genética , Secuencia de Bases , Brasil , Cadenas HLA-DRB1 , Cadenas HLA-DRB5 , Haplotipos , Humanos , Datos de Secuencia Molecular , Homología de SecuenciaRESUMEN
HLA class II genes are strongly associated with susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). The present study reports the HLA-DRB1 genotyping of 41 IDDM patients and 99 healthy subjects from the Southeast of Brazil (Campinas region). Both groups consisted of an ethnic mixture of Caucasian, African Negro and Amerindian origin. HLA-DRB1*03 and *04 alleles were found at significantly higher frequencies among IDDM patients compared to the controls (DRB1*03: 48.8 percent vs 18.2 percent, P<0.005, RR= 4.27); DRB1*04:43.9 percent vs 15.1 percent, P<0.008, RR=4.37) and were associated with a susceptibility to the disease. DRB1*03/*04 heterozygosity conferred a strong IDDM risk (RR=5.44). In contrast, the HLA-DRB1*11 allele frequency was lower among IDDM patients (7.3 percent vs 26.3 percent in controls), but the difference was not significant. These data agree with those described for other populations and allow genetic characterization of IDDM in Brazil.