Anticorpos antígeno-específicos como biomarcadores de resposta imune na hanseníase

Abstract

Leprosy is a chronic granulomatous disease that, although curable, still carries great prejudice and stigma. It’s caused by the intracellular bacillus Mycobacterium leprae and mainly affects the skin and peripheral nerves, resulting in sensory and motor impairment, with characteristic deformities and disabilities. In 2017, Brazil registered 26,875 new cases of the disease (12.8% of the world total), a fact that keeps it as the second country in absolute numbers, losing only to India. The diagnosis of leprosy is essentially clinical, but serological tests can contribute to its early detection and help in the classification of the diseases forms. In this work we evaluated the humoral immune response profile of patients with paucibacillary and multibacillary leprosy forms and their household contacts, using the enzyme-linked immunosorbent assay (ELISA) for the detection of IgM, IgG, IgA and IgE antibodies, reactive against recombinant antigens NDO-HSA, LID-1 and NDO-LID. Additionally, the effect of single dose rifampicin chemoprophylaxis on serum levels of anti-NDO-HSA, anti-LID-1 and anti-NDO-LID IgA antibodies in domiciliary contacts of multibacillary leprosy cases was analyzed. The results show that patients with the multibacillary form present increased levels of IgM, IgG and IgA antibodies against the three antigens tested, when compared to paucibacillary patients and healthy controls. In contrast, IgE responses to NDO-HSA, LID-1 and NDO-LID were greatly reduced even with lower serum dilution and higher antigen concentration. The reactivity of IgM antibodies was higher against NDO-HSA and NDO-LID antigens, whereas reactivity of IgG antibodies was higher against LID-1 and NDO-LID antigens. Elevated serum levels of IgA antibodies against the three antigens tested were detected in about 72 to 100% of multibacillary patients. There was also a significant reactivity of paucibacillary patients (63%) to NDO-HSA antigen. Analysis of the ROC curves confirmed the good performance of the antigens in the diagnosis of multibacillary leprosy, with a better performance of anti-NDO-LID IgG and anti-NDO-HSA IgA. The ELISA-IgM, ELISA-IgG and ELISA-IgA ELISA tests weren’t able to differentiate household contacts of multibacillary patients, compared to the contacts of paucibacillary cases or in comparison with the healthy controls of the endemic area, despite a tendency to increase of anti-NDO-HSA IgA reactivity in the CMB group. Single dose rifampicin chemoprophylaxis reduced discrete anti-NDO-HSA IgA antibody titers in multibacillary patient contacts. The results confirm the good performance of the NDO-HSA, LID-1 and NDO-LID antigens in leprosy serodiagnosis, and suggest that the search for IgA against the synthetic analogue NDO-HSA may be an additional tool in the diagnosis of clinical forms of the disease . The application of serological tests involving anti-NDO-HSA IgA screening in the follow-up of household contacts suspected of subclinical infection and who received prophylactic treatment with rifampicin deserves further investigation.