SOD1 plasma level as a biomarker for therapeutic failure in cutaneous leishmaniasis

Abstract

We show that increased plasma superoxide dismutase 1 (SOD1) levels are statistically significant predictors of the failure of pentavalent antimony treatment for cutaneous leishmaniasis caused by Leishmania braziliensis. In Leishmania amazonensis-infected patients, host SOD1 levels can be used to discriminate between localized and drug-resistant diffuse cutaneous leishmaniasis. Using in situ transcriptomics (nCounter), we demonstrate a significant positive correlation between host SOD1 and interferon α/β messenger RNA (mRNA) levels, as well as interkingdom correlation between host SOD1 and parasite SOD2/4 mRNA levels. In human macrophages, in vitro treatment with SOD1 increases the parasite burden and induces a diffuse cutaneous leishmaniasis-like morphology. Thus, SOD1 is a clinically relevant biomarker and a therapeutic target in both localized and diffuse cutaneous leishmaniasis.

Keywords: Biomarker; Cutaneous leishmaniasis; Diffuse cutaneous leishmaniasis; Interkingdom signaling; Leishmania amazonensis; Leishmania braziliensis; Oxidative burst; Parasite escape mechanism; Superoxide dismutase; Therapeutic failure.