Avaliação de polimorfismos genéticos das moléculas coestimulatórias CD80 e CD86 em pacientes portadores de hanseníase

Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that is influenced by host genetic. The poles of the leprosy are occupied by spectrum immunological opposite of the tuberculoid one hand, predominantly of the Th1 immune response and the other by the lepromatous, with predominant Th2 immune response. During the development of immune response, beyond antigen-specific signal is necessary a second signal for activation of T lymphocytes, termed costimulation. This signal can be delivered by costimulatory molecules CD80 and CD86 present on cell surfaces of antigen presented. The binding of these molecules to the receptors CD28 and CTLA-4 T lymphocytes present in the leads to the activation or inhibition of immune response, respectively. The down-regulation of CD80 and CD28 in patients with lepromatous leprosy, and lepromatous borderline can be responsible for defective signaling T cell specific for the antigens of M. leprae through CD80/CD28. This can lead to clonal inactivation of T cells reactive to antigens of M. leprae, and consequently, the bacillus grows without restraint in macrophages. In this work we investigated the possible relationship between this polymorphism in the CD80 and CD86 genes with susceptibility to leprosy and/or clinical forms of the disease. Genotyping of polymorphisms was performed by direct sequencing. CD80 were analyzed six gene SNPs located in the gene promoter region (-454 C/A, -387 T/C, -232 G/A, -79 C/G,-7 T/C and +5 C/A) and Polymorphism insertion/deletion (-557_-561 CATGA) and the CD86 gene was analyzed a SNP in exon 8, position +1057 G/A. For the CD86 gene was observed a similar genotype distribution among leprosy patients and control subjects, and the genotypes G/G and G/A the most prevalent in both populations. There were also no significant differences between the allelic and genotypic frequencies among leprosy patients and healthy controls regarding the polymorphisms of the CD80 gene. Although CD80 and CD86 have important functions in the immune response data obtained in this study demonstrate that the analyzed polymorphisms do not influence the susceptibility to leprosy and/or different clinical forms of leprosy.