Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase

Abstract

Leprosy is a chronic infectious disease with a slow clinical evolution, caused by the intracellular bacillus Mycobacterium leprae. This disease can be classified according to operational forms in paucibacillary and multibacillary, or according to histopathological criteria in the forms: indeterminate, tuberculoid, dimorphic and virchowian. In the clinical evolution of the disease, patients may present complications such as leprosy reactions and the occurrence of physical disability. The clinical manifestations and complications of leprosy are related to several factors such as the genetic background and immunological aspects inherent to the host. However, the exact role of cytokines in the characteristics of leprosy is still unclear. Therefore, the objective of this research was to investigate the role of cytokines in the complications and clinical forms of leprosy. 104 patients diagnosed with leprosy and their contact controls (n = 70) participated in the research. These were classified according to the clinical and operational form of the disease, as well as the occurrence of leprosy reaction and physical disability. After blood collection and serum separation, the dosage of cytokines of the profiles Th1, Th2, Treg, Th17, Th9 and Th22 produced by patients and contacts using the Luminex technique was observed. Statistical analyzes were performed using the Graphpad Prisma software and the cluster formation was performed using the R program (3.6.0). We observed that cytokines of inflammatory profile IL-12p70, IFN-y, TNF- α and IL-18 were related to the virchowian form, as well as being linked to the occurrence of leprosy and physical disability. The cytokines IL-17 and IL-22 was associated with the tuberculoid form. As for the cluster analysis, it was observed the formation of a cluster formed by the cytokines IFN-γ, TNF-α, IL-9, IL-5, IL-10 and IL18 that are involved with the main complications of leprosy. On the other hand, there was formation of the cluster composed of the cytokines IL-12p70, IL-1β, IL-23, IL-5, IL-2 and IL-17A in CC, this cluster may be related to an effective immune response against M. leprae. We conclude that cytokines of the Th1 profile (IFN-y, TNF-α e IL18) are involved with leprosy complications. In addition, we identified cytokines (TNFα, IL-18, IL-4, IL-6, IL-10 e IL-27) involved in the occurrence of leprosy complications, which can function as biomarkers for monitoring the clinical course of the disease.