Papel das células B e dos anticorpos na patogênese da hanseníase e das reações hansênicas

Abstract

Leprosy is a spectral disease caused by Mycobacterium leprae infection. Subjects 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 occurrence of leprosy reactions: reversal reaction (RR) and erythema nodosum leprosum (ENL). These reactions occur predominantly in MB patients. Our aim 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 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. More than 82% of the household contacts recruited in the study had been previously exposed to M. leprae infection, with a potential risk of developing leprosy. This finding shows that the quantification of specific antibodies in the blood can be used to define groups at risk for leprosy development. MB subjects 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. 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. During ENL, there is an expansion in the plasmoblast population, however a decrease in the concentration of these immunoglobulins in the blood. Patients with elevated levels of anti-LID-NDO antibody at diagnosis presented a 20- fold increased risk of developing reactions. Our results show that the use of recombinant antigens in serological tests can contribute to an early diagnosis, decreasing the risk of M. leprae transmission. The exacerbated humoral immune response of MB patients may be explained, at least in part, by 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 reaction. Clinically, this is an important data since it can direct future therapeutic interventions.