Banca de QUALIFICAÇÃO: FRANCIANNE MEDEIROS AMORIM

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : FRANCIANNE MEDEIROS AMORIM
DATA : 03/03/2017
HORA: 14:00
LOCAL: sala de reunioes do Instituto de Medicina Tropical (IMT)
TÍTULO:

Role of B cells and antibodies in pathogenesis of leprosy and its immune reactions

PALAVRAS-CHAVES:

Leprosy. Antibodies. B cells. Leprosy reactions.

PÁGINAS: 87
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 multiple disseminated lesions throughout the body and a high bacterial load (multibacillary - MB). The former present a strong cellular immune response and the latter have a predominantly humoral response. Despite reduction in leprosy’s global prevalence, Brazil is still 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 evaluate the role of B cells and antibodies in the pathogenesis of leprosy and its immune reactions. For this, we aim to: 1. Determine the profile of specific antibodies to the recombinant antigens LID-1 and LID-NDO in people exposed to M. leprae infection. 2. Analyze 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. The results showed 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 (LID-1, r = 0.84, p˂0.001, LID-NDO, r = 0.82, p ˂0.001). Most 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 can be used to define groups at risk for the development of disease among household contacts. MB patients presented an exacerbated humoral immune response which was associated with numerical and functional alterations in B cells, with increased frequency of plasmoblast (PB: 5.6%; MB: 7.4%, p= 0.038) and reduced expression of CD32 in these cells (PB: 83.9%; MB: 77.7%, p= 0.0082). MB patients presented higher concentrations of IgG1 (842.8mg/dL, p=0.0289) and IC (757.2μg/Eq/mL, p= 0.006) in the blood when compared to PB (IgG1=697.3mg/dL; IC=434μg/Eq/mL). During ENL there is an expansion in the plasmoblast population, however a decrease in the concentration of these immunoglobulins in the blood. This decrease may be a consequence of the deposition of IC in other tissues. In a 2-years cohort, it was observed that MB patients that developed ENL (during or after multidrug therapy) presented increased levels of IgM (278.3mg/dL, p=0.0004), IgG1 (1059md/dL, p=0.0257), specific antibodies (OD=0.9246, p=0.022), and IC (1180μg/Eq/mL, p=0.019) in the blood, when compared to those that did not develop reactions (IgM=69.53 mg/dL; IgG1= 786mg/dL; OD= 0.5975; IC=491.6 μg/Eq/mL). Patients with elevated levels of anti-LID-NDO antibody, at diagnosis, presented a 16-fold increased risk of developing ENL. Clinically, this is an important data since it can direct future therapeutic interventions in order to prevent the development of reactions.

MEMBROS DA BANCA:
Presidente - 1549705 - ADRIANA FERREIRA UCHOA
Externo ao Programa - 1674643 - MARCOS ROMUALDO COSTA
Externo à Instituição - MAURICIO LISBOA NOBRE - UFRN