Marcadores imunológicos para detecção de hanseníase subclínica: resposta imune aos antígenos LID-1 e PGL-1

Abstract

Leprosy is a neglected, slow-progressing disease with highly diverse clinical forms, making diagnosis challenging and often inconclusive or delayed, allowing the development of disabilities and deformities in patients. This ancient and stigmatizing disease recorded 140.594 new cases globally in 2021, with Brazil ranking second. Control measures are based on diagnosis, treatment, and contact surveillance. However, this disease requires more innovative approaches for complete control. Therefore, this study proposes to define immunological biomarkers for detecting subclinical leprosy using the antigens LID-1 and PGL-1. The study was conducted on a large scale through a bead-based multiplex assay (MBA-Multiplex Beaded Assay and Rapid Test for anti-PGL-1) to evaluate immunological aspects within the investigated communities. The study allowed for the prospective monitoring of the groups based on the presence of anti-LID-1 and anti-PGL-1 serological antibodies, as well as examining other biomarkers through the analysis of cytokines and chemokines via flow cytometry in the supernatant of in vitro peripheral blood mononuclear cell (PBMC) cultures. This project design enabled an advanced approach to studying the immune profile of individuals exposed to leprosy who reside in hyperendemic areas in Eastern Minas Gerais, Brazil. In this study, 1.200 individuals were selected, 79 of whom tested positive for LID-1 [LID-1 (+)]; 76 LID-1(-) individuals matched by sex and age were selected from the remainder. The PGL-1 test showed 47 individuals with positive results [PGL-1 (+)] and 104 with negative results [PGL-1 (-)]. Results demonstrated that the LID-1 (+) group exhibited a heightened inflammatory response with elevated levels of IFN- and CXCL10. The PGL-1 (-) group also showed increased CXCL10 associated with a moderate inflammatory reaction. In the integrated analysis of the LID-1 (+) vs PGL-1 (-) groups, a more intense inflammatory profile was observed, with increased IFN-, CXCL10, TNF, IL-17, and IL-2. These findings highlight the role of immune mediators such as CXCL10, IFN-, and TNF and underscore the relevance of multiplex assays in detecting specific immune profiles. The study contributes to developing improved diagnostic methods, which, once validated, could strengthen epidemiological surveillance and clinical management of leprosy in high-endemicity regions.