Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis
Autor: | Daniel P. Beiting, Ba T. Nguyen, Edgar M. Carvalho, Fernanda O. Novais, Phillip Scott, Camila Farias Amorim, Lucas P. Carvalho, Ana M. Misic |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Leishmaniasis Cutaneous CD8-Positive T-Lymphocytes Parasite load Leishmania braziliensis Parasite Load Article Variable Expression Transcriptome 03 medical and health sciences 0302 clinical medicine Cutaneous leishmaniasis medicine Humans Gene Skin Cell Death biology business.industry Gene Expression Profiling Leishmaniasis General Medicine medicine.disease biology.organism_classification Killer Cells Natural Gene expression profiling Treatment Outcome 030104 developmental biology Gene Expression Regulation Immunology business 030215 immunology |
Zdroj: | Sci Transl Med |
ISSN: | 1946-6242 1946-6234 |
Popis: | 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. |
Databáze: | OpenAIRE |
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