title: 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.
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia Faculty of Medicine, Federal University of Bahia, Bahia Department of Microbiology and Immunology K. U. Leuven, Rega Institute for Medical Research, Leuven, Belgium.
authors: Ricardo
authors: R
authors: Khouri
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia.
authors: Gilvaneia Silva
authors: GS
authors: Santos
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia.
authors: George
authors: G
authors: Soares
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia.
authors: Jackson M
authors: JM
authors: Costa
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia Faculty of Medicine, Federal University of Bahia, Bahia Institute for Investigation in Immunology, INCT, São Paulo, Brazil.
authors: Aldina
authors: A
authors: Barral
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia Faculty of Medicine, Federal University of Bahia, Bahia Institute for Investigation in Immunology, INCT, São Paulo, Brazil.
authors: Manoel
authors: M
authors: Barral-Netto
authors: LIMI, LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia Department of Microbiology and Immunology K. U. Leuven, Rega Institute for Medical Research, Leuven, Belgium.
authors: Johan
authors: J
authors: Van Weyenbergh
mesh_terms: D000328:Adult; D000965:Antimony / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D013482:Superoxide Dismutase / Q000097:blood*; D000072105:Superoxide Dismutase-1; D017211:Treatment Failure
chemical_list: D000981:Antiprotozoal Agents; D015415:Biomarkers; C000606290:SOD1 protein, human; D000965:Antimony; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Biomarker; Cutaneous leishmaniasis; Diffuse cutaneous leishmaniasis; Interkingdom signaling; Leishmania amazonensis; Leishmania braziliensis; Oxidative burst; Parasite escape mechanism; Superoxide dismutase; Therapeutic failure