Banca de QUALIFICAÇÃO: TATIANA KUMMER DA ROCHA PINHEIRO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : TATIANA KUMMER DA ROCHA PINHEIRO
DATA : 11/09/2017
HORA: 08:00
LOCAL: Sala de Reuniões do Instituto de Medicina Tropical
TÍTULO:

Susceptibility to leprosy and reactional forms in a population at Rio Grande do Norte

PALAVRAS-CHAVES:

Leprosy. M. leprae. Erythema Nodosum Leprosum. Reversal reaction. Immunochip.

PÁGINAS: 58
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

        Leprosy is a chronic, slowly evolving infectious disease with a broad spectrum of clinical manifestations caused by Mycobacterium leprae. The State of RN is constantly presenting new cases, with some locations showing high detection rates, such as the city of Mossoró with a detection rate of 39.73 per 100,000 habitants in 2012. After exposure to the bacillus, only about 10% of the patients progress to disease. After the disease develops, the patient may obtain a spontaneous cure or develop one of five clinical forms. Depending on the level of susceptibility and the way in which the patient develops the immune response against mycobacteria, infection may result in one of the reactional states. Post-infection evolution with M. leprae is also influenced by the genetic repertoire of the host, being considered a complex disease in which characteristics of the host and the environment are as important as the characteristics of the pathogen to determine the evolution of the disease. Therefore, in order to contribute to the knowledge of the association of genetic factors to susceptibility to leprosy, the objective of the present study is to analyze polymorphisms associated with susceptibility to leprosy in a population of RN. Therefore, the study was divided into two parts: phenotypic characterization and genotypic characterization of a newborn population. Firstly, the phenotypic characterization was performed based on the collection of data regarding patients and household contacts, and the detection of anti-LID-NDO antibodies from Elisa. The amount of antibodies varied according to the operational classification of the case and the type of reaction, being higher in MB cases and type II reaction. In addition, most of the household contacts obtained a negative ELISA result, but when compared contacts of PB and MB, positivity increased in the latter group (11% and 36%, respectively) due to contact with a larger number of bacilli. Secondly, the genotypic characterization was performed using Immunochip, with the analysis of SNPs associated in three groups: leprosy vs communicants, reaction vs non-reaction, and LID-NDO antibody rate. Among the SNPs associated with leprosy vs household contacts, some were related to immune response (FASLG, TNFS18, EBF1 and ICOSLG), in addition to a SNP close to VDR, vitamin D receptor is important in leprosy due to its role in immunomodulation associated with vitamin D3 in activated monocytes, macrophages and lymphocytes. In the reaction vs. non-reaction group, we observed the association of several SNPs on chromosome 6 near genes known as susceptibility to psoriasis. Psoriasis and leprosy are diseases with autoimmune profiles, which explains why they have shared susceptibility genes. Among these genes is the CCHCR1, overexpressed in keratinocytes in psoriatic lesions, regulated by IFN-γ. In the continuous LID-NDO antibody rate results, analysis of associated SNPs revealed association with THEMIS gene, which encodes a regulatory protein in T-cell selection.

MEMBROS DA BANCA:
Externo ao Programa - 2323511 - ADRIANA AUGUSTO DE REZENDE
Presidente - 1549705 - ADRIANA FERREIRA UCHOA
Externo ao Programa - 1714243 - DANIELLA REGINA ARANTES MARTINS SALHA