CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Estudos em diferentes populaÃÃes tÃm mostrado que a vacinaÃÃo com a BCG concede proteÃÃo parcial contra a hansenÃase. Entretanto, a necessidade da revacinaÃÃo e seu impacto na resposta imune contra antÃgenos do Mycobacterium leprae à pouco compreendida, principalmente nas crianÃas que sÃo contatos destes pacientes com hansenÃase, e constituem uma populaÃÃo de risco para o adoecimento. Neste estudo, investigamos o papel da revacinaÃÃo com a BCG na modulaÃÃo da resposta imune em contatos menores de quinze anos de pacientes com hansenÃase. Amostras de sangue perifÃrico de vinte e cinco crianÃas, vacinadas com a BCG ao nascer, foram coletas antes e dois meses apÃs a revacinaÃÃo com a BCG. Suas cÃlulas mononucleares (PBMC) foram estimuladas com proteÃnas e peptÃdeos do M. leprae, dosando-se as quantidades de IFN-γ e IL-10 por ELISA. Anteriormente a revacinaÃÃo, foram coletas amostras para dosagem de IgM e IgG anti-PGL-1 e realizado o teste tuberculÃnico (PPD) para avaliaÃÃo da eficÃcia vacinal apÃs a revacinaÃÃo. Identificamos o potencial papel da BCG em estimular a produÃÃo de IFN-γ e/ou IL-10 dependendo do antÃgeno e da idade do contato, sem relaÃÃo com o PPD e sorologia anti-PGL-1. Estes resultados sugerem que a BCG modula a resposta imune dos contatos frente aos antÃgenos do M. leprae, com o frequente aumento nos nÃveis de IFN-γ, frente ao MLT, nas crianÃas com idade entre 1 a 4 anos (4.203 + 539,2 pg/mL prÃ-BCG x 9.141 + 860,9 pg/mL pÃs-BCG, p=0,001). Jà os contatos entre 5 a 9 anos mostram aumento na produÃÃo de IL-10 (210 +39,4 pg/mL prÃ-BCG x 680 + 76,74 pg/mL pÃs-BCG, p=0,001) e IFN-γ (4.912 + 1.065 pg/mL x 9.249 + 1.171 pg/mL, p=0,024). Estes achados sÃo acompanhados com o aumento dos casos de hansenÃase em crianÃas entre 5 a 9 anos na comunidade. Entretanto, nos contatos entre 10 a 15 anos a revacinaÃÃo falha em induzir o aumento de IFN-γ e IL-10. Os contatos de MB produziram, simultaneamente, altos nÃveis de IFN-γ e IL-10 em resposta ao MLT, enquanto que os contatos de PB somente produziram altos nÃveis de IFN-γ apÃs a revacinaÃÃo. A produÃÃo de IFN-γ e IL-10 frente aos peptÃdeos sintÃticos p38 e p69 indica que estes antÃgenos podem ser possÃveis marcadores de infecÃÃo. Assim, a BCG pode ser protetora, sendo eficiente em induzir o aumento da resposta por IFN-γ nestes contatos, frente aos antÃgenos do M. leprae. / Studies in different populations have shown that vaccination with BCG provides partial protection against leprosy. However, need of boost BCG vaccination and your impact in response immune against antigens of Mycobacterium leprae is poorly understood, mainly in children who are contacts of these patients with leprosy, and constitute population of risk for illness. This study, we investigated the paper a second dose of BCG given to contacts of leprosy patients under the age of fifteen years in modulate the response imune. Blood samples of twenty five children, who received a first dose of BCG at birth, were collected immediately before and two months after BCG revaccination. Your peripheral blood mononuclear cells (PBMC) stimulated by proteins and peptides of M. leprae, were measured IFN-γ and IL-10 by an ELISA assay. Before revaccination the serum anti-PGL1 IgG and IgM isotypes were measured by ELISA assays performed with native PGL1- coated microplates, and PPD-skin reaction was measured 2 to 3 months after revaccination. The study was approved by the local Ethic Committee, number 006-08, May 7th, 2008. BCG revaccination can induces IFN-gamma and/or IL-10 production related to antigen and age, but did not correlated with PPD-skin reaction or anti-PGL1 levels. The PBMCâs production of IFN-gamma against MLT (total M. leprae antigen) after BCG was higher on children under 4 years old (N= 8, 4203,0  539,2 pg/mL before BCG x 9141,0  860,9 pg/mL after BCG, p=0,015, Mann-Whitneyâs test). Children between 5 and 9 years old showed an increase either of IFN-gama levels (N=11, 4912  1065 pg/mL x 9249,0  1171 pg/mL, p=0,024, Mann-Whitneyâs test) or IL-10 levels (N=11, 210,6  39,4 pg/mL x 680,3  76,74 pg/mL, p=0, 0,001, Mann-Whitneyâs test). However children between 10 and 15 years old failed to increase the cytokines levels after BCG booster. Contacts of multibacillary patients produced higher IFN-gamma levels (N= 13, 4536,0  543,1 pg/mL x 9263,0  989,0 pg/mL, p=0,0012, Mann-Whitneyâs test) and IL-10 levels (N= 13, 235,9  46,5 pg/mL x 743,5  87,8, p=0,0012, Mann-Whitneyâs test) against MLT after BCG, but only IFN-gamma levels (N=12, 4975,0  995,8 pg/mL x 8126,0  788,6, p=0,0342, Mann-Whitneyâs test) increased after BCG on contacts of paucibacillary patients. The production of IFN-gamma and IL-10 against two synthetic peptides (p38 and p67), before and after BCG vaccine, were similar as seen with MLT antigen, but the absence of cytokine production against p69 help to identify this peptide as a effective diagnostic marker.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:5012 |
| Date | 13 May 2010 |
| Creators | Emerson Ramalho Ferreira |
| Contributors | LÃlia Maria Carneiro CÃmara, Aparecida Tiemi NagÃo Dias |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em Microbiologia MÃdica, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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