Mixed T helper1/T helper2/T cytotoxic profile in subjects with chronic Chagas disease with hypersensitivity reactions to benznidazole

CASTRO EIRO, MD; NATALE MA; ALVAREZ MG; CASTRO A; SEIGELSHIFER D; VIOTTI R; FERNANDEZ M; MAZZUOCCOLO L; LOCOCO B; BERTOCCHI G; CESAR G; ALBAREDA MC; ELIAS MJ; CAPUTO MB; GADDI E; BALBARYSKI J; VIGLIANO CA; LAUCELLA S

Microbiology spectrum

American Society for Microbiology

Año: 2022

2165-0497

Background. Dermatitis is the most severe adverse event during treatment with benznidazole in chronic Chagas disease, which is probably mediated by T cells. A set of molecules representative of the different Type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of T. cruzi-infected subjects presenting dermatitis during benznidazole administration. Methods. Through cytometric bead assays and ELISA capture techniques, the serum levels of cytokines, chemokines, pro-apoptotic molecules and mediators of activation and migration of eosinophils and T cells were measured in T. cruzi-infected subjects who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37). Results. Serum levels of IL-5, soluble Fas cell surface death receptor ligand and interferon γ-induced protein significantly increased, either independently or concomitantly, at 7-30 days post-treatment with benznidazole and decreased thereafter, in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis compared with those without dermatitis. In the skin biopsies two clear patterns emerged, a Th1/T cytotoxic and a Th2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein, glutamic-oxaloacetic transaminase and uremia levels and T cell activation emerged as risk factors for development of dermatitis during benznidazole administration. Conclusions. These results support a delayed-type hypersensitivity reaction to benznidazole, with the involvement of CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for a better management of adverse drug reactions to benznidazole.