Reconhecimento de padrões moleculares, clínicos e imunológicos para criação de algoritmo da suscetibilidade e evolução clínica da Hanseníase baseado em inteligência artificial.

Abstract

Leprosy is an active transmission disease and is characterized by heterogeneity of clinical manifestations - from the tuberculoid pole (TT) to the Virchowian (LL) - which are correlated with the host cell-mediated immune response against the causing Mycobacterium leprae. The Type Th-1 immune response in patients with the TT or paucibacillary form is effective in limiting the clinical disease. On the other hand, the clinical form LL or multibacillary is characterized by low cell-mediated immunity with a humoral response by the activation of Th-2 cells. The role of host genetic factors in the development of leprosy has been well established through epidemiological indicators and genetic studies of the host in susceptibility to leprosy. The results of extensive genome analyzes (linkage and association) and studies of candidate genes suggest genetic control independent of both susceptibility to leprosy per se and the development of different clinical forms. In this work, we seek to evaluate the levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17) and chemokines (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10), genotyping single nucleotide polymorphisms (SNP) of the TLR4 genes (rs4986790, rs2149356, rs1927914, and rs2737190), IL-10 (rs1554286, rs3024490, rs1800872, and rs1800871), TLR1 (rs4833095), TLR2 (rs3804099), and SLC11A1 (rs17235416) of patients’ response of patients and their household contacts and associate them with clinical data on leprosy. A model based on textit Random Forest was also implemented, which allowed us, with about 97% accuracy, to predict the clinical evolution of household contacts by recognizing the pattern of their clinical and immunological variables. Besides, among other findings, an differential pattern of chemokines (especially IL-8 and RANTES) was found in cell culture stimulated by M. leprae when compared to culture without stimulation. A 2.3 times greater chance of illness was verified in the carriers of the G allele in the rs1927914 or rs2737190 variants of the TLR4 gene.