A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum
BackgroundIn the absence of a late marker of treatment failure or relapse in MDR-TB patients, biomarkers based on host-miRNAs coupled with M. tuberculosis-RNAs evaluated in extracellular vesicles (EVs) are an alternative follow-up for MDR-TB disease. Characterization of EVs cargo to identify differe...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:78d559b9be8447b4b3107884ecc751202021-11-04T07:43:22ZA Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum1664-322410.3389/fimmu.2021.760468https://doaj.org/article/78d559b9be8447b4b3107884ecc751202021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.760468/fullhttps://doaj.org/toc/1664-3224BackgroundIn the absence of a late marker of treatment failure or relapse in MDR-TB patients, biomarkers based on host-miRNAs coupled with M. tuberculosis-RNAs evaluated in extracellular vesicles (EVs) are an alternative follow-up for MDR-TB disease. Characterization of EVs cargo to identify differentially expressed miRNAs before and after treatment, and to identify M. tuberculosis-derived RNA in serum EVs from resistant TB patients.MethodsEVs were isolated from serum of 26 drug-resistant TB (DR-TB) patients and 16 healthy subjects. Differential expression of miRNAs in pooled exosomes from both untreated and treated patients was assessed and individually validated at different time points during treatment. In addition, M. tuberculosis RNA was amplified in the same samples by qPCR.ResultsA multivariate analysis using miR-let-7e-5p, -197-3p and -223-3p were found to be a more sensitive discriminator between healthy individuals and those with TB for both DR-TB (AUC= 0.96, 95%, CI=0.907-1) and MDR-TB groups (AUC= 0.95, 95%, CI= 0.89-1). Upregulation of miR-let-7e-5p were observed at the time of M. tuberculosis negative culture T(3-5) for MDR-TB group or for long-term T(9-15) for MDR-TB group without diabetes (T2DM). A second pathogen-based marker based on 30kDa and 5KST sequences was detected in 33% of the MDR-TB patients after the intensive phase of treatment. The miR-let7e-5p is a candidate biomarker for long-term monitoring of treatment for the group of MDR-TB without T2DM. A dual marker of host-derived miR-let7e-5p and M. tuberculosis-derived RNA for monitoring-TB treatment based in serum EVs.ConclusionA dual marker consisting of host-derived miR-let7e-5p and M. tuberculosis-derived RNA, could be an indicator of treatment failure or relapse time after treatment was completed.Claudia CarranzaMaría Teresa HerreraSilvia Guzmán-BeltránManuel Guadalupe Salgado-CantúIvan Salido-GuadarramaElizabeth SantiagoLeslie Chávez-GalánLuis Horacio Gutiérrez-GonzálezYolanda GonzálezFrontiers Media S.A.articledrug resistance to TBmiRNAsexosomesM. tuberculosis-RNAmonitoring treatmentImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
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| collection |
DOAJ |
| language |
EN |
| topic |
drug resistance to TB miRNAs exosomes M. tuberculosis-RNA monitoring treatment Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
drug resistance to TB miRNAs exosomes M. tuberculosis-RNA monitoring treatment Immunologic diseases. Allergy RC581-607 Claudia Carranza María Teresa Herrera Silvia Guzmán-Beltrán Manuel Guadalupe Salgado-Cantú Ivan Salido-Guadarrama Elizabeth Santiago Leslie Chávez-Galán Luis Horacio Gutiérrez-González Yolanda González A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum |
| description |
BackgroundIn the absence of a late marker of treatment failure or relapse in MDR-TB patients, biomarkers based on host-miRNAs coupled with M. tuberculosis-RNAs evaluated in extracellular vesicles (EVs) are an alternative follow-up for MDR-TB disease. Characterization of EVs cargo to identify differentially expressed miRNAs before and after treatment, and to identify M. tuberculosis-derived RNA in serum EVs from resistant TB patients.MethodsEVs were isolated from serum of 26 drug-resistant TB (DR-TB) patients and 16 healthy subjects. Differential expression of miRNAs in pooled exosomes from both untreated and treated patients was assessed and individually validated at different time points during treatment. In addition, M. tuberculosis RNA was amplified in the same samples by qPCR.ResultsA multivariate analysis using miR-let-7e-5p, -197-3p and -223-3p were found to be a more sensitive discriminator between healthy individuals and those with TB for both DR-TB (AUC= 0.96, 95%, CI=0.907-1) and MDR-TB groups (AUC= 0.95, 95%, CI= 0.89-1). Upregulation of miR-let-7e-5p were observed at the time of M. tuberculosis negative culture T(3-5) for MDR-TB group or for long-term T(9-15) for MDR-TB group without diabetes (T2DM). A second pathogen-based marker based on 30kDa and 5KST sequences was detected in 33% of the MDR-TB patients after the intensive phase of treatment. The miR-let7e-5p is a candidate biomarker for long-term monitoring of treatment for the group of MDR-TB without T2DM. A dual marker of host-derived miR-let7e-5p and M. tuberculosis-derived RNA for monitoring-TB treatment based in serum EVs.ConclusionA dual marker consisting of host-derived miR-let7e-5p and M. tuberculosis-derived RNA, could be an indicator of treatment failure or relapse time after treatment was completed. |
| format |
article |
| author |
Claudia Carranza María Teresa Herrera Silvia Guzmán-Beltrán Manuel Guadalupe Salgado-Cantú Ivan Salido-Guadarrama Elizabeth Santiago Leslie Chávez-Galán Luis Horacio Gutiérrez-González Yolanda González |
| author_facet |
Claudia Carranza María Teresa Herrera Silvia Guzmán-Beltrán Manuel Guadalupe Salgado-Cantú Ivan Salido-Guadarrama Elizabeth Santiago Leslie Chávez-Galán Luis Horacio Gutiérrez-González Yolanda González |
| author_sort |
Claudia Carranza |
| title |
A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum |
| title_short |
A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum |
| title_full |
A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum |
| title_fullStr |
A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum |
| title_full_unstemmed |
A Dual Marker for Monitoring MDR-TB Treatment: Host-Derived miRNAs and M. tuberculosis-Derived RNA Sequences in Serum |
| title_sort |
dual marker for monitoring mdr-tb treatment: host-derived mirnas and m. tuberculosis-derived rna sequences in serum |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/78d559b9be8447b4b3107884ecc75120 |
| work_keys_str_mv |
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