RESUMEN
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.
Asunto(s)
Niño , Preescolar , Humanos , Masculino , Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación/genética , Proteínas Tirosina Quinasas/genética , Agammaglobulinemia/enzimología , Citometría de Flujo , Enfermedades Genéticas Ligadas al Cromosoma X/enzimología , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
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%. 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.
Asunto(s)
Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación/genética , Proteínas Tirosina Quinasas/genética , Agammaglobulinemia Tirosina Quinasa , Agammaglobulinemia/enzimología , Niño , Preescolar , Citometría de Flujo , Enfermedades Genéticas Ligadas al Cromosoma X/enzimología , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
OBJECTIVE: Hypergammaglobulinemia is an early manifestation of perinatal HIV infection. Our objective was to analyze the differences in serum immunoglobulin levels between infected and seroreverter children and their association with clinical outcome. METHODS: We carried out a historical prospective study with 107 infected and 90 seroreverter children. We compared the IgA, IgG, and IgM levels between infected and seroreverters in the first 18 months of life; IgA, IgG, and IgM as surrogate markers of infection; and IgA, IgG, and IgM levels in the first 5 years in infected children, according to clinical outcome. The Mann-Whitney test was used for comparison between groups. Surrogate markers were assessed according to sensitivity, specificity, positive and negative predictive values, and J index. RESULTS: Infected children, when compared to seroreverters, showed significantly higher levels of: IgM from the 1st to the 5th trimester; IgA and IgG from the 2nd to the 6th trimester (P /= 90 mg/dl in the 2nd trimester and IgG >/= 1,700 mg/ dl or 1,200 mg/dl in the 2nd and 3rd trimesters were associated with HIV infection with J indexes of 0.97, 0.92, and 0.93, respectively. Infected children in the B and C categories, compared to those in the N and A, showed higher levels of IgM from the 2nd to the 4th year, and IgA from the 3rd to the 5th year (P