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Previous issue date: 2015-03-31 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES === Introduction: Asthma is a disease that affects most children, characterized by inflammation and airway hyperresponsiveness. Asthma has two main phenotypes depending on the presence of atopy. In addition to Th2 cells, Th17 cells, Th1 and Treg cells are involved in disease pathology by secreting cytokines. CD4 T cells have plasticity, which are influenced by environmental and genetic factors.
Aim: To assess the phenotypic profile of CD4 T cells in asthmatic children of school age, with or without the presence of atopy and healthy controls and correlate the data with disease severity. In addition, analyze cells expressing more than one transcription factor in the blood of atopic asthmatic children to D.pteronyssinus stimulating mononuclear cells with DerP1 protein.
Methods: This was a cross-sectional case-control study, where 8-14 years-old asthmatic and healthy children were recruited of public schools in Porto Alegre/RS. Mononuclear cells were isolated by Histopaque peripheral blood of children and cultured with anti-CD3/CD28 or DerP1 protein. After 24 hours the cells were stained with antibodies specific for transcription factors for analysis of Th2, Th17, Th1 and Treg cells by flow cytometry. Moreover, it was analyzed in plasma allergen-specific IgE specific.
Results: The results showed that children with asthma have a higher frequency of CD4+ GATA-3+ compared to controls. Frequency of CD4+GATA-3+ROR?t+ cells correlated with disease severity, except with severe therapy resistant asthma (STRA). Atopic patients showed a higher proportion of co-expressing more than one transcription factor cells compared to non-atopic individuals. Stimulation with DerP1 protein enhances the frequency of CD4 + Foxp3 +ROR?t+ compared with the control and stimulation with anti-CD3/ CD28.
Conclusion: In general, the results presented in this thesis allowed us to conclude that the allergens play an important role in the development of cells expressing more than one transcription factor in atopic patients. In addition, our study was the first to demonstrate that STRA children have a distinct expression profile of regulatory transcription factors of CD4 T cells Th1, Th2, Th17 and Treg compared to other severity levels of the disease. === Introdu??o: A asma ? uma doen?a prevalente em crian?as, tendo como principal caracter?stica a inflama??o e hiperresponsividade das vias a?reas. Al?m das c?lulas Th2, as c?lulas Th17, Th1 e Treg s?o envolvidas na patologia da doen?a pela fun??o que elas e as citocinas por elas secretadas exercem. A asma apresenta dois fen?tipos principais, os quais dependem da presen?a de atopia. As c?lulas TCD4 apresentam plasticidade, que s?o influenciadas por fatores ambientais e gen?ticos.
Objetivos: Avaliar o perfil fenot?pico de c?lulas TCD4 de crian?as em idade escolar asm?ticas, com ou sem a presen?a de atopia e de controles saud?veis. Correlacionar os dados obtidos com a severidade da doen?a. Al?m disso, avaliar as c?lulas que co-expressam mais de um fator de transcri??o no sangue de crian?as asm?ticas at?picas para D.pteronyssinus estimulando as c?lulas com a prote?na Derp1.
Materiais e m?todos: Este foi um estudo transversal caso-controle, onde crian?as de 8 a 14 anos foram recrutadas de escolas p?blicas de Porto Alegre/RS, asm?ticas e controles. As c?lulas mononucleares foram isoladas por Histopaque do sangue perif?rico destas crian?as e colocadas em cultura com anti-CD3/CD28 ou com prote?na Derp1. Ap?s 24hs as c?lulas foram marcadas com anticorpos espec?ficos para os fatores de transcri??o para an?lise do perfil Th2, Th17, Th1 e Treg por citometria de fluxo. Al?m disto, foi analisado no plasma a IgE espec?fica para um painel de alergenos.
Resultados: Os resultados obtidos mostraram que as comparado com os controles. As c?lulas duplo-positivas CD4+GATA-3+ROR?t+ correlacionaram com o grau de severidade da doen?a, exceto com asma severa de dif?cil controle (ADC). Pacientes at?picos apresentaram uma propor??o maior de c?lulas co-expressando mais de um fator de transcri??o comparados com indiv?duos n?o-at?picos. Estimula??o de c?lulas provenientes de pacientes at?picos com a prote?na Derp1 aumenta a frequ?ncia de c?lulas CD4+Foxp3+ROR?t+ quando comparados com o controle e estimula??o com anticorpos anti-CD3 e anti-CD28.
Conclus?o: De uma maneira geral, os resultados apresentados nesta tese nos permitem concluir que os al?rgenos desempenham um papel importante no desenvolvimento das c?lulas que expressam mais de um fator de transcri??o em pacientes at?picos. Al?m disso, nosso estudo foi o primeiro a demonstrar que crian?as com ADC apresentam um perfil distinto de express?o de fatores de transcri??o reguladores de c?lulas TCD4 do tipo Th1, Th2, Th17 e Treg quando comparado com crian?as com doen?a menos severa.
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