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Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis.

ABSTRACT: Early diagnosis increases the treatment success rate for active tuberculosis (ATB) and decreases mortality. MicroRNAs (miRNAs) have been studied as blood-based markers of several infectious diseases. We performed miRNA profiling to identify differentially expressed (DE) miRNAs using whole blood samples from 10 healthy controls (HCs), 15 subjects with latent tuberculosis infection (LTBI), and 12 patients with ATB, and investigated the expression of the top six miRNAs at diagnosis and over the treatment period in addition to performing miRNA-target gene network and gene ontology analyses. miRNA profiling identified 84 DE miRNAs in patients with ATB, including 80 upregulated and four downregulated miRNAs. Receiver operating characteristic curves of the top six miRNAs exhibited excellent distinguishing efficiency with an area under curve (AUC) value > 0.85. Among them, miR-199a-3p and miR-6886-3p can differentiate between ATB and LTBI. Anti-TB treatment restored the levels of miR-199b-3p, miR-199a-3p, miR-16-5p, and miR-374c-5p to HC levels. Furthermore, 108 predicted target genes were related to the regulation of cellular amide metabolism, intrinsic apoptotic signaling, translation, transforming growth factor beta receptor signaling, and cysteine-type endopeptidase activity. The DE miRNAs identified herein are potential biomarkers for diagnosis and therapeutic monitoring in ATB.

SUBMITTER: Kim J

PROVIDER: S-EPMC8871062 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis.

Kim Junseong J Park Heechul H Park Sung-Bae SB Lee Eun Ju EJ Je Min-A MA Ahn Eunsol E Sim Bora B Lee Jiyoung J Jin Hyunwoo H Lee Kyung Eun KE Cho Sang-Nae SN Kang Young Ae YA Lee Hyejon H Kim Sunghyun S Kim Jungho J

Diagnostics (Basel, Switzerland) 20220201 2

Early diagnosis increases the treatment success rate for active tuberculosis (ATB) and decreases mortality. MicroRNAs (miRNAs) have been studied as blood-based markers of several infectious diseases. We performed miRNA profiling to identify differentially expressed (DE) miRNAs using whole blood samples from 10 healthy controls (HCs), 15 subjects with latent tuberculosis infection (LTBI), and 12 patients with ATB, and investigated the expression of the top six miRNAs at diagnosis and over the tre ...[more]

PMID: 35204460

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Project description:BackgroundNew diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB.MethodsRecombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals.ResultsA robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses.ConclusionThese results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB.

Dataset Information

Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis.

Publications

Identification of MicroRNAs as Potential Blood-Based Biomarkers for Diagnosis and Therapeutic Monitoring of Active Tuberculosis.

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