Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis
Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interfero...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/10/9/716 |
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| author | Workneh Korma Adane Mihret Yunhee Chang Azeb Tarekegn Metasebiya Tegegn Adem Tuha Dasom Hwang Mesfin Asefa Mahlet O. Hasen Seoyoung Kim Tesfaye S. Tessema Hyeyoung Lee |
| author_facet | Workneh Korma Adane Mihret Yunhee Chang Azeb Tarekegn Metasebiya Tegegn Adem Tuha Dasom Hwang Mesfin Asefa Mahlet O. Hasen Seoyoung Kim Tesfaye S. Tessema Hyeyoung Lee |
| author_sort | Workneh Korma |
| collection | DOAJ |
| description | Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^<sup>-ΔΔCt</sup>) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (<i>p</i> = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (<i>p</i> = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s). |
| first_indexed | 2024-03-10T16:14:02Z |
| format | Article |
| id | doaj.art-deea0556409148ce9cd368fa0b5ebacb |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T16:14:02Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-deea0556409148ce9cd368fa0b5ebacb2023-11-20T14:16:20ZengMDPI AGDiagnostics2075-44182020-09-0110971610.3390/diagnostics10090716Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active TuberculosisWorkneh Korma0Adane Mihret1Yunhee Chang2Azeb Tarekegn3Metasebiya Tegegn4Adem Tuha5Dasom Hwang6Mesfin Asefa7Mahlet O. Hasen8Seoyoung Kim9Tesfaye S. Tessema10Hyeyoung Lee11Molecular Diagnostic Laboratory, Department of Biomedical Laboratory Sciences, Yonsei University, Wonju 26493, KoreaArmauer Hansen Research Institute, Addis Ababa, P.O Box 1005, EthiopiaMolecular Diagnostic Laboratory, Department of Biomedical Laboratory Sciences, Yonsei University, Wonju 26493, KoreaArmauer Hansen Research Institute, Addis Ababa, P.O Box 1005, EthiopiaArmauer Hansen Research Institute, Addis Ababa, P.O Box 1005, EthiopiaArmauer Hansen Research Institute, Addis Ababa, P.O Box 1005, EthiopiaMolecular Diagnostic Laboratory, Department of Biomedical Laboratory Sciences, Yonsei University, Wonju 26493, KoreaSt. Paul’s Hospital Millennium Medical College, Department of pathology, Addis Ababa, P.O. Box 1271, EthiopiaArmauer Hansen Research Institute, Addis Ababa, P.O Box 1005, EthiopiaMolecular Diagnostic Laboratory, Department of Biomedical Laboratory Sciences, Yonsei University, Wonju 26493, KoreaInstitute of Biotechnology, Addis Ababa University, Addis Ababa, P.O. Box 1176, EthiopiaMolecular Diagnostic Laboratory, Department of Biomedical Laboratory Sciences, Yonsei University, Wonju 26493, KoreaTuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^<sup>-ΔΔCt</sup>) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (<i>p</i> = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (<i>p</i> = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).https://www.mdpi.com/2075-4418/10/9/716Tuberculosis diagnosiscytokine and chemokine biomarkerextrapulmonary tuberculosisgene expressionRT-PCRdiagnostics |
| spellingShingle | Workneh Korma Adane Mihret Yunhee Chang Azeb Tarekegn Metasebiya Tegegn Adem Tuha Dasom Hwang Mesfin Asefa Mahlet O. Hasen Seoyoung Kim Tesfaye S. Tessema Hyeyoung Lee Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis Diagnostics Tuberculosis diagnosis cytokine and chemokine biomarker extrapulmonary tuberculosis gene expression RT-PCR diagnostics |
| title | Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis |
| title_full | Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis |
| title_fullStr | Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis |
| title_full_unstemmed | Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis |
| title_short | Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis |
| title_sort | antigen specific cytokine and chemokine gene expression for diagnosing latent and active tuberculosis |
| topic | Tuberculosis diagnosis cytokine and chemokine biomarker extrapulmonary tuberculosis gene expression RT-PCR diagnostics |
| url | https://www.mdpi.com/2075-4418/10/9/716 |
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