Multi-omic Analyses of Plasma Cytokines, Lipidomics, and Transcriptomics Distinguish Treatment Outcomes in Cutaneous Leishmaniasis.

Abstract

SummaryLeishmania braziliensis infection frequently results in cutaneous leishmaniasis (CL). An increase in incidence of drug-resistant CL leading to treatment failure has been reported. Identification of reliable predictors of treatment outcomes is necessary to optimize patient care. Here, we performed a prospective case-control study in which plasma levels of cytokines and lipid mediators were assessed at different time points during antileishmanial therapy in patients with CL from Brazil. Multidimensional analyses were employed to describe a combination of biomarkers able to predict and characterize treatment failure. We found a biosignature influenced mainly by plasma levels of lipid mediators that accurately predicted treatment failure. Furthermore, transcriptomic analysis of a publicly available data set revealed that expression levels of genes related to lipid metabolism measured in skin lesions could distinguish treatment outcomes in CL. Thus, activation of pathways linked to lipid biosynthesis predicts treatment failure in CL. The biomarkers identified may be further explored as therapeutic targets.