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VARIABLE GENE EXPRESSION AND PARASITE LOAD PREDICT TREATMENT OUTCOME IN CUTANEOUS LEISHMANIASIS
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University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Pennsylvania, USA.
Resumen en ingles
Patients infected with Leishmania braziliensis develop chronic lesions that often fail to respond to treatment with antiparasite drugs. To determine whether genes whose expression is highly variable in lesions between patients might influence disease outcome, we obtained biopsies of lesions from patients before treatment with pentavalent antimony and performed transcriptomic profiling on these clinical samples. We identified genes that were highly variably expressed between patients, and the variable expression of these genes correlated with treatment outcome. Among the most variable genes in all the patients were components of the cytolytic pathway, and the expression of these genes correlated with parasite load in the skin. We demonstrated that treatment failure was linked to the cytolytic pathway activated during infection. Using a host-pathogen marker profile of as few as three genes, we showed that eventual treatment outcome could be predicted before the start of treatment in two separate cohorts of patients with cutaneous leishmaniasis (n = 21 and n = 25). These findings raise the possibility of point-of-care diagnostic screening to identify patients at high risk of treatment failure and provide a rationale for a precision medicine approach to drug selection in cutaneous leishmaniasis. This work more broadly demonstrates the value of identifying genes of high variability in other diseases to better understand and predict diverse clinical outcomes.
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