با سلام خدمت کاربران عزیز، به اطلاع می رساند ترجمه مقالاتی که سال انتشار آن ها زیر 2008 می باشد رایگان بوده و میتوانید با وارد شدن در صفحه جزییات مقاله به رایگان ترجمه را دانلود نمایید.
عنوان انگلیسی مقاله:
Host transcriptomic signature as alternative test-of-cure in visceral leishmaniasis patients co-infected with HIV
ترجمه فارسی عنوان مقاله:
امضای transcriptomic میزبان به عنوان گزینه درمانی جایگزین در بیماران لیشمانیوز احشایی آلوده به HIV
Sciencedirect - Elsevier - EBioMedicine, 55 (2020) 102748. doi:10.1016/j.ebiom.2020.102748
Wim Adriaensena,*, Bart Cuypersb,c, Carlota F. Corderoa, Bewketu Mengashad, Severine Blessone, Lieselotte Cnopsa, Paul M. Kayef, Fabiana Alvese, Ermias Dirod, Johan van Griensvena
Visceral leishmaniasis (VL) treatment in HIV patients very often fails and is followed by high
relapse and case-fatality rates. Hence, treatment efficacy assessment is imperative but based on invasive
organ aspiration for parasite detection. In the search of a less-invasive alternative and because the host
immune response is pivotal for treatment outcome in immunocompromised VL patients, we studied changes
in the whole blood transcriptional profile of VL-HIV patients during treatment.
Methods: Embedded in a clinical trial in Northwest Ethiopia, RNA-Seq was performed on whole blood samples
of 28 VL-HIV patients before and after completion of a 29-day treatment regimen of AmBisome or AmBisome/
miltefosine. Pathway analyses were combined with a machine learning approach to establish a
clinically-useful 4-gene set.
Findings: Distinct signatures of differentially expressed genes between D0 and D29 were identified for
patients who failed treatment and were successfully treated. Pathway analyses in the latter highlighted a
downregulation of genes associated with host cellular activity and immunity, and upregulation of antimicrobial
peptide activity in phagolysosomes. No signs of disease remission nor pathway enrichment were
observed in treatment failure patients. Next, we identified a 4-gene pre-post signature (PRSS33, IL10, SLFN14,
HRH4) that could accurately discriminate treatment outcome at end of treatment (D29), displaying an average
area-under-the-ROC-curve of 0.95 (CI: 0.751.00).
Interpretation: A simple blood-based signature thus holds significant promise to facilitate treatment efficacy
monitoring and provide an alternative test-of-cure to guide patient management in VL-HIV patients.
Funding: Project funding was provided by the AfricoLeish project, supported by the European Union Seventh
Framework Programme (EU FP7).
Keywords: Visceral leishmaniasis | HIV | RNA signature | Treatment efficacy | Blood signature