Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient

Abstract A comprehensive assessment of immunological profiles during HIV-TB co-infection is essential to predict mortality, and facilitate the development of effective diagnostic assays, therapeutic agents, and vaccines. Expression levels of 105 immune-related genes were measured at enrolment and 6t...

Full description

Bibliographic Details
Main Authors: Gebremedhin Gebremicael, Atsbeha Gebreegziabxier, Desta Kassa
Format: Article
Language:English
Published: Nature Portfolio 2022-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-14305-8
_version_ 1811343647169314816
author Gebremedhin Gebremicael
Atsbeha Gebreegziabxier
Desta Kassa
author_facet Gebremedhin Gebremicael
Atsbeha Gebreegziabxier
Desta Kassa
author_sort Gebremedhin Gebremicael
collection DOAJ
description Abstract A comprehensive assessment of immunological profiles during HIV-TB co-infection is essential to predict mortality, and facilitate the development of effective diagnostic assays, therapeutic agents, and vaccines. Expression levels of 105 immune-related genes were measured at enrolment and 6th month follow-up from 9 deceased HIV and TB coinfected patients who died between 3 and 7th months follow-up and at enrolment, 6th and 18th month from 18 survived matched controls groups for 2 years. Focused gene expression profiling was assessed from peripheral whole blood using a dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Eleven of the 105 selected genes were differentially expressed between deceased individuals and survivor-matched controls at baseline. At baseline, IL4δ2 was significantly more highly expressed in the deceased group than survivor matched controls, whereas CD3E, IL7R, PTPRCv1, CCL4, GNLY, BCL2, CCL5, NOD1, TLR3, and NLRP13 had significantly lower expression levels in the deceased group compared to survivor matched controls. At baseline, a non-parametric receiver operator characteristic curve was conducted to determine the prediction of mortality of single genes identified CCL5, PTPRCv1, CD3E, and IL7R with Area under the Curve of 0.86, 0.86, 0.86, and 0.85 respectively. The expression of these genes in the survived control was increased at the end of TB treatment from that at baseline, while decreased in the deceased group. The expression of PTPRCv1, CD3E, CCL5, and IL7R host genes in peripheral blood of patients with TB-HIV coinfected can potentially be used as a predictor of mortality in the Ethiopian setting. Anti-TB treatment might be less likely to restore gene expression in the level expression of the deceased group. Therefore, other new therapeutics that can restore these genes (PTPRCv1, CD3E, IL7R, and CCL5) in the deceased groups at baseline might be needed to save lives.
first_indexed 2024-04-13T19:33:37Z
format Article
id doaj.art-ad7b37821ac04de4a35774020eba8f7c
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-04-13T19:33:37Z
publishDate 2022-06-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-ad7b37821ac04de4a35774020eba8f7c2022-12-22T02:33:07ZengNature PortfolioScientific Reports2045-23222022-06-0112111010.1038/s41598-022-14305-8Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patientGebremedhin Gebremicael0Atsbeha Gebreegziabxier1Desta Kassa2Ethiopian Public Health Institute (EPHI)Ethiopian Public Health Institute (EPHI)Ethiopian Public Health Institute (EPHI)Abstract A comprehensive assessment of immunological profiles during HIV-TB co-infection is essential to predict mortality, and facilitate the development of effective diagnostic assays, therapeutic agents, and vaccines. Expression levels of 105 immune-related genes were measured at enrolment and 6th month follow-up from 9 deceased HIV and TB coinfected patients who died between 3 and 7th months follow-up and at enrolment, 6th and 18th month from 18 survived matched controls groups for 2 years. Focused gene expression profiling was assessed from peripheral whole blood using a dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Eleven of the 105 selected genes were differentially expressed between deceased individuals and survivor-matched controls at baseline. At baseline, IL4δ2 was significantly more highly expressed in the deceased group than survivor matched controls, whereas CD3E, IL7R, PTPRCv1, CCL4, GNLY, BCL2, CCL5, NOD1, TLR3, and NLRP13 had significantly lower expression levels in the deceased group compared to survivor matched controls. At baseline, a non-parametric receiver operator characteristic curve was conducted to determine the prediction of mortality of single genes identified CCL5, PTPRCv1, CD3E, and IL7R with Area under the Curve of 0.86, 0.86, 0.86, and 0.85 respectively. The expression of these genes in the survived control was increased at the end of TB treatment from that at baseline, while decreased in the deceased group. The expression of PTPRCv1, CD3E, CCL5, and IL7R host genes in peripheral blood of patients with TB-HIV coinfected can potentially be used as a predictor of mortality in the Ethiopian setting. Anti-TB treatment might be less likely to restore gene expression in the level expression of the deceased group. Therefore, other new therapeutics that can restore these genes (PTPRCv1, CD3E, IL7R, and CCL5) in the deceased groups at baseline might be needed to save lives.https://doi.org/10.1038/s41598-022-14305-8
spellingShingle Gebremedhin Gebremicael
Atsbeha Gebreegziabxier
Desta Kassa
Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient
Scientific Reports
title Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient
title_full Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient
title_fullStr Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient
title_full_unstemmed Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient
title_short Low transcriptomic of PTPRCv1 and CD3E is an independent predictor of mortality in HIV and tuberculosis co-infected patient
title_sort low transcriptomic of ptprcv1 and cd3e is an independent predictor of mortality in hiv and tuberculosis co infected patient
url https://doi.org/10.1038/s41598-022-14305-8
work_keys_str_mv AT gebremedhingebremicael lowtranscriptomicofptprcv1andcd3eisanindependentpredictorofmortalityinhivandtuberculosiscoinfectedpatient
AT atsbehagebreegziabxier lowtranscriptomicofptprcv1andcd3eisanindependentpredictorofmortalityinhivandtuberculosiscoinfectedpatient
AT destakassa lowtranscriptomicofptprcv1andcd3eisanindependentpredictorofmortalityinhivandtuberculosiscoinfectedpatient