Avalia????o de polimorfismos gen??ticos de L12RB2 e IFN-y em pacientes portadores de hansen??ase

• Author(s): Silva, George Allan Villarouco da
• Date: 2016
• Origin: Oasisbr
• Subject(s): Hansen??ase; Imunidade celular; Citocina; Polimorfismo; Leprosy; Cellular immunity; Cytokine; Polymorphism; CIENCIAS BIOLOGICAS: IMUNOLOGIA: IMUNOLOGIA CELULAR
• Document Type: Master thesis
• Language: Portuguese

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CAPES - Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior

Leprosy is an infectious disease characterized by different clinical forms that are associated with the type of immune response against Mycobacterium leprae. Polymorphisms present in the first intron of IFN-??? may have an important role in the regulation of the immune response, which could have functional consequences for gene transcription. Later studies identified the present of five polymorphisms in the IL12RB2 promoter region, this polymorphisms will may transcriptional factor suppress IL12R???2 expression affect the development of cellular immune response. In the present study we investigated a possible association of the +874 T/A SNP and IFN-???, microsatellite and polymorphisms present in the IL12RB2 promoter region associated with susceptibility to leprosy or with development of clinical forms in patients from brazilian Legal Amazon states. Nucleotide sequencing was performed with samples from 118 leprosy patients and 114 controls subjects, as well as immunophenotyping of CD4 +, CD8 + and CD69 + T cells by flow cytometry. Between leprosy patients and controls subjects, as well as between PB and MB patients were no observed significant differences among the studied genotypes in the polymorphisms of IL12RB2 studies. The polymorphisms -1035, -1023 and -464 present an absolute correlation (p<0.0001) having a combination of a same genotype in this positions. The microsatellite encoding 16 CA repeats was significantly associated with PB compared to MB patients (p = 0.019), being individuals homozygous for the +874 A allele present IFN-??? and the mean level of CD4 + and CD69 + T cells were higher. Our data suggest that polymorphisms present in the first intron of IFN-??? and of the IL12RB2 promoter region are not associated with susceptibility to leprosy, nevertheless, the +874 A/A genotype and microsatellite encoding 16 CA repeats may be related to a higher cellular immune response in patients and are consistently more frequently detected in PB patients.

A hansen??ase ?? uma doen??a infecciosa caracterizada por apresentar diferentes formas cl??nicas que est??o associadas com o tipo de resposta imune ao Mycobacterium leprae. Polimorfismos gen??ticos presentes no primeiro ??ntron de IFN-??? podem apresentar importante papel na regula????o da resposta imune, podendo resultar em consequ??ncias funcionais na transcri????o do gene. Estudos anteriores identificaram a presen??a de cinco polimorfismos na regi??o promotora de IL12RB2, sendo que estes polimorfismos poderiam suprimir fatores de transcri????o na express??o de IL12R???2, afetando o desenvolvimento da resposta imune celular. No presente estudo investigamos uma poss??vel associa????o do SNP +874, do microssat??lite de IFN-??? e de polimorfismos presentes na regi??o promotora de IL12RB2 com a susceptibilidade ?? hansen??ase ou com desenvolvimento das formas cl??nicas em pacientes dos Estados da Amaz??nia Legal brasileira. O sequenciamento nucleot??dico foi realizado em 118 pacientes com hansen??ase e 114 indiv??duos controles, assim como a imunofenotipagem de c??lulas T CD4 +, CD8 + e CD69 + pela citometria de fluxo. Entre pacientes com hansen??ase e indiv??duos controles, assim como entre pacientes PB e MB n??o foram observadas diferen??as significativas entre os gen??tipos estudados nos polimorfismos de IL12RB2. Os polimorfismos - 1035, -1023 e -464 apresentam uma correla????o absoluta (p<0,0001) havendo combina????o de um mesmo gen??tipo nas respectivas posi????es. O microssat??lite com 16 repeti????es foi significativamente associado com pacientes PB quando comparado aos pacientes MB (p = 0,019). Indiv??duos homozig??ticos ao alelo +874 A apresentaram maiores n??veis de IFN-??? e maior m??dia de c??lulas T CD4 + e CD69 +. Nossos dados sugerem que polimorfismos presentes no primeiro ??ntron de IFN-??? e da regi??o promotora de IL12RB2 n??o est??o associados com a susceptibilidade ?? hansen??ase. No entanto, o gen??tipo +874 A/A e 16 repeti????es de CA de IFN-??? podem estar relacionados ?? alta resposta imune celular observada nestes pacientes, sendo tamb??m mais frequentemente encontrados em pacientes PB.