Immunodeficiency and immune activation in juvenile systemic lupus erythematosus, in HIV infection and in vertical exposure to human immunodeficiency virus

Introdução: O uso da terapia de alta potência tem aumentado a sobrevida dos pacientes infectados pelo HIV e permitido uma reconstituição imune desses indivíduos. A avaliação dessa reconstituição imune e suas consequências são de especial relevância para crianças e adolescentes. Métodos: Avaliamos 41 crianças e adolescentes infectados, com idade de 6 a 21 anos e 25 crianças e adolescentes sadios não expostos ao HIV, com idade semelhante (Controle). O grupo HIV foi dividido em HIV Indetectável (Carga Viral 400cópias/mL). Foi realizada imunofenotipagem dos linfócitos, incluindo avaliação de ativação imune e apoptose através de CD38 QuantiBRITE e caspase-3 ativa, respectivamente. Imunoglobulinas (IgA, IgG, IgM) e anticorpos contra sarampo e tétano também foram avaliados. Resultados: Pacientes infectados pelo HIV apresentaram menor expressão de CD28 em células T em relação aos indivíduos do grupo Controle (CD4+CD28+ - Controle: 98.3%. vs. HIV Indetectável: 96.3%. Tukey, p=0.02. CD8+CD28+ - Controle: 70.4%, HIV Indetectável: 56.7%, HIV Detectável: 50.3%. Controle vs. HIV Indetectável e Controle vs. HIV Detectável. Tukey, p=0.01 para ambas comparações). A média de CD38/célula T CD8+ foi mais elevada no HIV Detectável quando comparado com HIV Indetectável e Controle (Controle: 1725.8, HIV Indetectável: 1638.5, HIV Detectável: 3502.0. Controle vs. HIV Indetectável e Controle vs. HIV Detectável. Tukey, p=0.01 para ambas comparações). HIV Detectável teve níveis de apoptose mais elevados em células T CD8+ do que o HIV Indetectável (HIV Indetectável: 4.8% vs. HIV Detectável: 10.2%. Tukey, p=0.03). Os grupos HIV tiveram menores títulos de anticorpos contra sarampo e tétano do que o grupo Controle (Sarampo – Controle: 0.86 UI/mL vs. HIV Detectável: 0.05 UI/mL. Tukey. p=0.01. Tétano: Controle: 0.88 UI/mL vs. HIV Detectável: 0.14 UI/mL. Tukey. p=0.03). Conclusões: Mesmo após uso da terapia de alta potência, crianças e adolescentes infectados pelo HIV mantêm ativação imune e apoptose de células T CD8+, assim como baixa expressão de CD28, o que pode contribuir para uma baixa resposta a antígenos vacinaisBackground: The use of HAART has increased the life time of HIV-infected individuals and permitted an immune reconstitution. Assessing that immune restoration and its consequences is especially relevant for children and adolescents. Methods: We evaluated 41 HIV-infected children and adolescents aged 6 to 21 years, and 25 age-matched healthy non HIV-exposed children and adolescents (Control). HIV group was divided in HIV Undetectable (Viral Load400copies/mL). Immunophenotyping of lymphocytes was performed, including immune activation and apoptosis evaluation using CD38 QuantiBRITE and activated caspase-3, respectively. Immunoglobulins (IgA, IgG, IgM) and measles and tetanus antibodies were also measured. Results: HIV-infected patients had lower percentage of CD28 expression on T cells than Control group (CD4+CD28+ - Control: 98.3%. vs. HIV Undetectable: 96.3%. Tukey, p=0.02. CD8+CD28+ - Control: 70.4%, HIV Undetectable: 56.7%, HIV Detectable: 50.3%. Control vs. HIV Undetectable and Control vs. HIV Detectable. Tukey, p=0.01 for both comparison). CD38 molecules/CD8+ T cell were higher in HIV Detectable when compared with HIV Undetectable and Control (Control: 1725.8, HIV Undetectable: 1638.5, HIV Detectable: 3502.0. Control vs. HIV Undetectable and Control vs. HIV Detectable. Tukey, p=0.01 for both comparison). HIV Detectable had higher apoptosis levels in CD8+ T than HIV Undetectable (HIV Undetectable: 4.8% vs. HIV Detectable: 10.2%. Tukey, p=0.03). HIV had lower measles and tetanus antibodies than Control group (Measles – Control: 0.86 IU/mL vs. HIV Detectable: 0.05 IU/mL. Tukey. p=0.01. Tetanus: Control: 0.88 IU/mL vs. HIV Detectable: 0.14 IU/mL. Tukey. p=0.03). Background: The use of HAART has increased the life time of HIV-infected individuals and permitted an immune reconstitution. Assessing that immune restoration and its consequences is especially relevant for children and adolescents. Methods: We evaluated 41 HIV-infected children and adolescents aged 6 to 21 years, and 25 age-matched healthy non HIV-exposed children and adolescents (Control). HIV group was divided in HIV Undetectable (Viral Load400copies/mL). Immunophenotyping of lymphocytes was performed, including immune activation and apoptosis evaluation using CD38 QuantiBRITE and activated caspase-3, respectively. Immunoglobulins (IgA, IgG, IgM) and measles and tetanus antibodies were also measured. Results: HIV-infected patients had lower percentage of CD28 expression on T cells than Control group (CD4+CD28+ - Control: 98.3%. vs. HIV Undetectable: 96.3%. Tukey, p=0.02. CD8+CD28+ - Control: 70.4%, HIV Undetectable: 56.7%, HIV Detectable: 50.3%. Control vs. HIV Undetectable and Control vs. HIV Detectable. Tukey, p=0.01 for both comparison). CD38 molecules/CD8+ T cell were higher in HIV Detectable when compared with HIV Undetectable and Control (Control: 1725.8, HIV Undetectable: 1638.5, HIV Detectable: 3502.0. Control vs. HIV Undetectable and Control vs. HIV Detectable. Tukey, p=0.01 for both comparison). HIV Detectable had higher apoptosis levels in CD8+ T than HIV Undetectable (HIV Undetectable: 4.8% vs. HIV Detectable: 10.2%. Tukey, p=0.03). HIV had lower measles and tetanus antibodies than Control group (Measles – Control: 0.86 IU/mL vs. HIV Detectable: 0.05 IU/mL. Tukey. p=0.01. Tetanus: Control: 0.88 IU/mL vs. HIV Detectable: 0.14 IU/mL. Tukey. p=0.03). Conclusion: Even after HAART, HIV-infected children and adolescents maintain immune activation and apoptosis on CD8+ T cells, as well as low CD28 expression which can contribute to the poor humoral immune response to vaccine antigens.TEDEBV UNIFESP: Teses e dissertaçõe