Banca de DEFESA: FRANCIANNE MEDEIROS AMORIM

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : FRANCIANNE MEDEIROS AMORIM
DATA : 28/04/2017
HORA: 14:00
LOCAL: Sala Carl Peter von Dietrich
TÍTULO:

Role of B cells and antibodies in the pathogenesis of leprosy and leprosy immune reactions.

PALAVRAS-CHAVES:

Plasmoblasts. Immunoglobulin. Reversal reaction. Erythema nodosum leprosum.

PÁGINAS: 102
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

Leprosy is a spectral disease caused by Mycobacterium leprae infection. Patients can present single lesions with a reduced number of bacilli (paucibacillary - PB), but also disseminated lesions and a high bacterial load (multibacillary - MB). The former present a strong cellular immune response and the latter have a predominantly humoral response. Brazil is the second country in number of cases, with hyperendemic areas in several states, including Rio Grande do Norte. Disease’s high morbidity is directly associated with the intercurrence of leprosy reactions: reversal reaction (RR) and erythema nodosum leprosum (ENL). These reactions occur predominantly in MB patients. Our aims was to determine the role of B cells and antibodies in the pathogenesis of leprosy and its immune reactions, for this, the work was subdivided in two studies: 1. Determination of the profile of specific antibodies to the recombinant antigens LID-1 and LID-NDO according to the clinical spectrum of the disease and in household contacts. 2. Analysis of physiological changes involved in the regulation of antibody production in B cells of patients with different clinical forms of leprosy. For this latter, the frequency of different B cell subpopulations, the expression of CD32 and CD21 in these cells, subclasses of immunoglobulins present in the blood, immune complexes (IC) and proteins involved in the classical pathway of complement activation were evaluated. In the study 1, it was observed a gradual increase in the level of specific antibodies along with the clinical spectrum of the disease, and this increase was correlated with the bacterial index of the patients. More than 82% of the household contacts recruited in the study were previously exposed to M. leprae infection, and were, therefore, at risk of developing leprosy. Cohort performed in a hyperendemic region showed that the quantification of specific antibodies in the blood could be used to define groups at risk for the development of disease among household contacts. MB patients presented an exacerbated humoral immune response that was associated with numerical and functional alterations in B cells, with increased frequency of plasmoblast and reduced expression of CD32 in these cells. MB patients presented higher concentrations of IgG1 and IC in the blood when compared to PB. During ENL, there is an expansion in the plasmoblast population, however a decrease in the concentration of these immunoglobulins in the blood. In a 2-years cohort, it was observed that MB patients that developed ENL (during or after multidrug therapy) presented increased levels of IgM, IgG1, specific antibodies, and IC in the blood, when compared to those that did not develop reactions. Patients with elevated levels of anti-LID-NDO antibody at diagnosis presented a 16-fold increased risk of developing ENL. Our results show that the use of recombinant antigens in serological tests can contribute to an early diagnosis of leprosy, especially among household contacts, contributing to the control of the disease in endemic areas. The exacerbated humoral immune response of MB patients may explain, at least in part, by physiological changes in B cells. The quantification of anti-M. leprae antibodies and IgM and IgG1 subclasses at leprosy diagnosis may contribute to identify individuals at risk of developing ENL. Clinically, this is an important data since it can direct future therapeutic interventions.

MEMBROS DA BANCA:
Interno - 1549705 - ADRIANA FERREIRA UCHOA
Externo à Instituição - EUZENIR NUNES SARNO - Fiocruz - RJ
Externo à Instituição - JOHN DONELSON - UIOWA
Externo ao Programa - 1674643 - MARCOS ROMUALDO COSTA
Presidente - 350647 - SELMA MARIA BEZERRA JERONIMO