RESUMO
Mutations in Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in peripheral blood. We evaluated 5 male Brazilian patients, ranging from 3 to 10 years of age, from unrelated families, whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2 percent. BTK gene analysis was carried out using PCR-SSCP followed by sequencing. We detected three novel (Ala347fsX55, I355T, and Thr324fsX24) and two previously reported mutations (Q196X and E441X). Flow cytometry revealed a reduced expression of BTK protein in patients and a mosaic pattern of BTK expression was obtained from mothers, indicating that they were XLA carriers.
Assuntos
Criança , Pré-Escolar , Humanos , Masculino , Agamaglobulinemia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação/genética , Proteínas Tirosina Quinases/genética , Agamaglobulinemia/enzimologia , Citometria de Fluxo , Doenças Genéticas Ligadas ao Cromossomo X/enzimologia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
The causes of high morbidity due to infection among children with sickle-cell disease (SD) are unknown. Immunlogical studies have focused on spleen function, on the alternative complement pathway, and recently on phagocytic activity. We evaluated Fc recptor-mediated phagocytic activity. We evaluated Fc receptor-mediated phagocytosis (sheep red cells opsonized with rabbit anti-E IgG, EA) and C3b receptor-mediated phagocytosis (zymosan particles incubated with fresh serum) in 27 children with SD. The control group consisted of 28 normal children matched by age and sex. The phagocytic indices obtained for cells from patients with SD were significantly lower than those for the controls (P < 0.001), both when EA and zymosan were used independent of whether the zymosan particles were incubated with patient serum or with a pool of normal sera. The results suggest the absence of abnormalities in the alternative complement pathway but do indicate an intrinsic cellular defect