RESUMEN
Two novel HLA alleles DRB1*11:261 and DRB1*13:286 have nonsynonymous mutations in exon 2.
Asunto(s)
Cadenas HLA-DRB1 , Alelos , Brasil , Exones/genética , Cadenas HLA-DRB1/genética , HumanosRESUMEN
Several candidate gene studies have demonstrated that genetic polymorphisms in cytokine genes contribute to variations in the levels of cytokines produced and this variation may influence the occurrence and severity of complications after stem cell transplantation (HSCT). In this work we compared the serum concentrations of TNF-α, IFN-γ, IL-6, IL-10, and TGF-β1 in 13 recipients following HSCT with the TNF-308, IFNG+874, IL6-174, IL10-1082,-819,-592, and TGFB1+869,+915 polymorphisms. Serum cytokine levels were assessed using commercial ELISA kits for TNF-α, IFN-γ, IL-6, IL-10, and TGF-β1 (BioSource®, Nivelles, Belgium, Europe). Donor/recipient genotypes for these cytokine polymorphisms were analyzed by polymerase chain reaction-sequence-specific primer (PCR-SSP) with the Cytokine Genotyping Primers Kit (One Lambda , Canoga Park, CA, USA). We found correlation between the levels of IL-6 and IL-10 concentrations following HSCT and the IL6-174 and IL10-1082,-819,-592 polymorphisms, but not for other cytokines investigated in this study. Those with genotypes associated with low production of IL-6 and IL-10 produced lower levels of these cytokines than those with genotypes associated with high or intermediate production of these cytokines (P < 0.05).
Estudos de vários genes candidatos têm demonstrado que polimorfismos genéticos em genes de citocinas contribuem com variações nos níveis de citocinas produzidas e esta variação pode influenciar a ocorrência e gravidade de complicações após o transplante de células-tronco hematopoéticas (TCTH). Neste trabalho comparamos as concentrações séricas de TNF-α, IFN-γ, IL-6, IL-10 e TGF-β 1 em 13 receptores seguindo o TCTH com os polimorfismos TNF-308, IFNG+874, IL6-174, IL10-1082,-819,-592 e TGFB1+869,+915. Os níveis séricos de citocinas foram medidos usando-se kits comerciais de ELISA para TNF-α, IFN-γ, IL-6, IL-10 e TGF-β 1 (BioSource®, Nivelles, Belgium, Europe). Os genótipos de doadores/receptores para estes polimorfismos de citocinas foram analisados pela reação em cadeia da polimerase com sequências específicas de primer (PCR-SSP) com o kit Cytokine Genotyping Primers (One Lambda, Canoga Park, CA, USA). Encontramos correlação entre os níveis de IL-6 e IL-10 seguindo o TCTH e os polimorfismos IL6-174 e IL10-1082,-819,-592, mas não para outras citocinas investigadas neste estudo. Aqueles com genótipos relativos à baixa produção de IL-6 e IL-10 produziram mais baixos níveis destas citocinas que aqueles com genótipos relativos à produção alta e/ou intermediária destas citocinas (P < 0,05).
Asunto(s)
Trasplante de Médula Ósea , Polimorfismo Genético , Donantes de Tejidos , Ensayo de Inmunoadsorción Enzimática , Factores de Crecimiento Transformadores , Reacción en Cadena de la Polimerasa , Citocinas , Interleucina-6 , Interleucina-10 , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre , Genotipo , Enfermedad Injerto contra HuéspedRESUMEN
BACKGROUND: Neonatal thrombocytopenia (NT) occurs in 0.5 to 0.9% of unselected Caucasian newborns. However, the prevalence of this complication in other populations is unknown. In this study the prevalence/causes of NT was determined in Brazilian newborns, a population characterized by admixture among Indigenous, Africans, and Caucasians. STUDY DESIGN: A prospective study was carried out in a 3-year period, to determine the prevalence and causes of thrombocytopenia in cord blood samples. Genotyping for HPA 1-5 systems was performed in pairs of mother/neonates with and without thrombocytopenia. All mothers with genotypic mismatches from each group were tested for HPA-specific antibody using the MAIPA technique to identify alloimmunization. RESULTS: Platelet counts <100 x 10(9)/L were detected in 1.5% of 9,332 unselected newborns. In 0.15%, platelet count was <50 x 10(9)/L. Clinically significant bleeding was rare. Underlying diseases were present in 48% of the thrombocytopenic cases. HPA 1-5 system genotype mismatches occurred in 50% of gestations, but did not predict the risk for thrombocytopenia. Notably, mismatched genotypes for HPA-5 were slightly increased in the thrombocytopenic group. The presence of anti-HPA-5b antibodies was observed in 0.05% of unselected pregnancies, but increased to 12% among mothers of neonates with thrombocytopenia and mismatched genotype (N = 51). CONCLUSIONS: Neonatal thrombocytopenia is common among Brazilian newborns at rates comparable with those described among Caucasians. These data suggest that screening for genotypic HPA mismatch, followed by an HPA-specific immunoassay system, particularly for the HPA-5 system, among mothers of newborns with thrombocytopenia in our population would allow the identification of pregnancies at risk of alloimmune thrombocytopenia.