Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection
BackgroundLatent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to fals...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359555/full |
| _version_ | 1797272615546519552 |
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| author | Weicong Ren Zichun Ma Qiang Li Rongmei Liu Liping Ma Cong Yao Yuanyuan Shang Xuxia Zhang Mengqiu Gao Shanshan Li Yu Pang |
| author_facet | Weicong Ren Zichun Ma Qiang Li Rongmei Liu Liping Ma Cong Yao Yuanyuan Shang Xuxia Zhang Mengqiu Gao Shanshan Li Yu Pang |
| author_sort | Weicong Ren |
| collection | DOAJ |
| description | BackgroundLatent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals.MethodsParticipants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples.ResultsA total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance.ConclusionThe MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection. |
| first_indexed | 2024-03-07T14:30:56Z |
| format | Article |
| id | doaj.art-51e9824a4e7c46afaf66ea00f5cbcaef |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T14:30:56Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-51e9824a4e7c46afaf66ea00f5cbcaef2024-03-06T04:34:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13595551359555Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infectionWeicong Ren0Zichun Ma1Qiang Li2Rongmei Liu3Liping Ma4Cong Yao5Yuanyuan Shang6Xuxia Zhang7Mengqiu Gao8Shanshan Li9Yu Pang10Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, ChinaBackgroundLatent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals.MethodsParticipants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples.ResultsA total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance.ConclusionThe MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359555/fulltuberculosislatent tuberculosischemokinebiomarkerIGRA |
| spellingShingle | Weicong Ren Zichun Ma Qiang Li Rongmei Liu Liping Ma Cong Yao Yuanyuan Shang Xuxia Zhang Mengqiu Gao Shanshan Li Yu Pang Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection Frontiers in Immunology tuberculosis latent tuberculosis chemokine biomarker IGRA |
| title | Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection |
| title_full | Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection |
| title_fullStr | Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection |
| title_full_unstemmed | Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection |
| title_short | Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection |
| title_sort | antigen specific chemokine profiles as biomarkers for detecting mycobacterium tuberculosis infection |
| topic | tuberculosis latent tuberculosis chemokine biomarker IGRA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359555/full |
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