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Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB
Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plas...
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| Published in: | Journal of microbiology, immunology and infection immunology and infection, 2024-12, Vol.57 (6), p.937-946 |
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| container_end_page | 946 |
| container_issue | 6 |
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| container_title | Journal of microbiology, immunology and infection |
| container_volume | 57 |
| creator | López-Suárez, Andrea Santos-Sebastián, Mar Hernanz-Lobo, Alicia Rincón-López, Elena Aguilera-Alonso, David Saavedra-Lozano, Jesús Ruiz Serrano, María Jesús Hernández-Bartolomé, Ángel Medrano de Dios, Luz María Jiménez Fuentes, José Luis Navarro, María Luisa Tebruegge, Marc Santiago-García, Begoña |
| description | Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children.
We analyzed 17 biomarkers in 15 non–M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead–based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups.
Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non–MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p |
| doi_str_mv | 10.1016/j.jmii.2024.07.011 |
| format | article |
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We analyzed 17 biomarkers in 15 non–M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead–based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups.
Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non–MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p < 0.001) and a significant correlation between IL-2 and IL-1ra (r = 0.92), IL-21 (r = 0.91), MCP-3 (r = 0.84), and MMP-1 (r = 0.85). The IFN-γ/MCP-1 ratio was the most accurate biomarker combination for differentiating between MTB-infected and non–MTB-infected children (AUC, 0.82; sensitivity, 87.9%; specificity, 66.6%; p < 0.001) and between active TB and non–MTB-infected children (AUC 0.82; sensitivity 88.0%; specificity 60.0%; p < 0.001). None of the biomarkers investigated were able to discriminate between LTBI and active TB.
Our data suggest that combining the analyses of multiple biomarkers in plasma has the potential to enhance diagnosis of TB in children and, thus, warrants additional investigation. In particular, the diagnostic potential of IFN-γ/MCP-1 ratios should be further explored in larger pediatric cohorts.</description><identifier>ISSN: 1684-1182</identifier><identifier>ISSN: 1995-9133</identifier><identifier>EISSN: 1995-9133</identifier><identifier>DOI: 10.1016/j.jmii.2024.07.011</identifier><identifier>PMID: 39271436</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Adolescent ; Biomarkers ; Biomarkers - blood ; Chemokine CCL2 - blood ; Child ; Child, Preschool ; Cytokines - blood ; Diagnosis ; Female ; Humans ; Infant ; Inflammation - blood ; Interferon-gamma - blood ; Interleukin-2 - blood ; Interleukins - blood ; Latent Tuberculosis - blood ; Latent Tuberculosis - diagnosis ; Male ; Mycobacterium tuberculosis ; Pediatrics ; Sensitivity and Specificity ; Tuberculosis ; Tuberculosis - blood ; Tuberculosis - diagnosis</subject><ispartof>Journal of microbiology, immunology and infection, 2024-12, Vol.57 (6), p.937-946</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2621-3a47c68e568e027bcfd7379d7d0624de5b9aadb921d984efcee9e957aa3b33803</cites><orcidid>0009-0006-4497-0318 ; 0000-0002-4125-0423 ; 0000-0003-3717-5384 ; 0000-0003-1986-9016 ; 0000-0001-9618-5027 ; 0000-0002-9560-9104 ; 0000-0002-0982-1636</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39271436$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>López-Suárez, Andrea</creatorcontrib><creatorcontrib>Santos-Sebastián, Mar</creatorcontrib><creatorcontrib>Hernanz-Lobo, Alicia</creatorcontrib><creatorcontrib>Rincón-López, Elena</creatorcontrib><creatorcontrib>Aguilera-Alonso, David</creatorcontrib><creatorcontrib>Saavedra-Lozano, Jesús</creatorcontrib><creatorcontrib>Ruiz Serrano, María Jesús</creatorcontrib><creatorcontrib>Hernández-Bartolomé, Ángel</creatorcontrib><creatorcontrib>Medrano de Dios, Luz María</creatorcontrib><creatorcontrib>Jiménez Fuentes, José Luis</creatorcontrib><creatorcontrib>Navarro, María Luisa</creatorcontrib><creatorcontrib>Tebruegge, Marc</creatorcontrib><creatorcontrib>Santiago-García, Begoña</creatorcontrib><title>Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB</title><title>Journal of microbiology, immunology and infection</title><addtitle>J Microbiol Immunol Infect</addtitle><description>Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children.
We analyzed 17 biomarkers in 15 non–M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead–based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups.
Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non–MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p < 0.001) and a significant correlation between IL-2 and IL-1ra (r = 0.92), IL-21 (r = 0.91), MCP-3 (r = 0.84), and MMP-1 (r = 0.85). The IFN-γ/MCP-1 ratio was the most accurate biomarker combination for differentiating between MTB-infected and non–MTB-infected children (AUC, 0.82; sensitivity, 87.9%; specificity, 66.6%; p < 0.001) and between active TB and non–MTB-infected children (AUC 0.82; sensitivity 88.0%; specificity 60.0%; p < 0.001). None of the biomarkers investigated were able to discriminate between LTBI and active TB.
Our data suggest that combining the analyses of multiple biomarkers in plasma has the potential to enhance diagnosis of TB in children and, thus, warrants additional investigation. In particular, the diagnostic potential of IFN-γ/MCP-1 ratios should be further explored in larger pediatric cohorts.</description><subject>Adolescent</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Chemokine CCL2 - blood</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cytokines - blood</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Inflammation - blood</subject><subject>Interferon-gamma - blood</subject><subject>Interleukin-2 - blood</subject><subject>Interleukins - blood</subject><subject>Latent Tuberculosis - blood</subject><subject>Latent Tuberculosis - diagnosis</subject><subject>Male</subject><subject>Mycobacterium tuberculosis</subject><subject>Pediatrics</subject><subject>Sensitivity and Specificity</subject><subject>Tuberculosis</subject><subject>Tuberculosis - blood</subject><subject>Tuberculosis - diagnosis</subject><issn>1684-1182</issn><issn>1995-9133</issn><issn>1995-9133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNp9kctu1TAQhiNERUvLC7BAWbJJ8C1xLLGBcqtUqZt2bU3syZFDbAc7B6lvj8MpXbKw7LH_-cYzf1W9paSlhPYf5nb2zrWMMNES2RJKX1QXVKmuUZTzl-XcD6KhdGDn1eucZ0IEZ13_qjrnikkqeH9R4RcHhxDz5ky9xg3D5mCp41Sb6EcXXDjU6wLZQz266CH9xJT3583lfMTagocD1hBs7cK0gPewuRhKUK9oHWypcO8_X1VnEywZ3zztl9XDt6_31z-a27vvN9efbhvDekYbDkKafsCuLMLkaCYruVRWWtIzYbEbFYAdFaNWDQIng6hQdRKAj5wPhF9WNyeujTDrNbny40cdwem_FzEdNKTS6oIabGdGqrCbUAkCe8WeMSUmaYUkZCis9yfWmuKvI-ZNe5cNLgsEjMesOSWi48PQsyJlJ6lJMeeE03NpSvRulZ71bpXerdJE6mJVSXr3xD-OHu1zyj9viuDjSYBlYr8dJp2Nw2DKXBOarbTk_sf_A3grpZY</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>López-Suárez, Andrea</creator><creator>Santos-Sebastián, Mar</creator><creator>Hernanz-Lobo, Alicia</creator><creator>Rincón-López, Elena</creator><creator>Aguilera-Alonso, David</creator><creator>Saavedra-Lozano, Jesús</creator><creator>Ruiz Serrano, María Jesús</creator><creator>Hernández-Bartolomé, Ángel</creator><creator>Medrano de Dios, Luz María</creator><creator>Jiménez Fuentes, José Luis</creator><creator>Navarro, María Luisa</creator><creator>Tebruegge, Marc</creator><creator>Santiago-García, Begoña</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0009-0006-4497-0318</orcidid><orcidid>https://orcid.org/0000-0002-4125-0423</orcidid><orcidid>https://orcid.org/0000-0003-3717-5384</orcidid><orcidid>https://orcid.org/0000-0003-1986-9016</orcidid><orcidid>https://orcid.org/0000-0001-9618-5027</orcidid><orcidid>https://orcid.org/0000-0002-9560-9104</orcidid><orcidid>https://orcid.org/0000-0002-0982-1636</orcidid></search><sort><creationdate>202412</creationdate><title>Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB</title><author>López-Suárez, Andrea ; 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This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children.
We analyzed 17 biomarkers in 15 non–M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead–based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups.
Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non–MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p < 0.001) and a significant correlation between IL-2 and IL-1ra (r = 0.92), IL-21 (r = 0.91), MCP-3 (r = 0.84), and MMP-1 (r = 0.85). The IFN-γ/MCP-1 ratio was the most accurate biomarker combination for differentiating between MTB-infected and non–MTB-infected children (AUC, 0.82; sensitivity, 87.9%; specificity, 66.6%; p < 0.001) and between active TB and non–MTB-infected children (AUC 0.82; sensitivity 88.0%; specificity 60.0%; p < 0.001). None of the biomarkers investigated were able to discriminate between LTBI and active TB.
Our data suggest that combining the analyses of multiple biomarkers in plasma has the potential to enhance diagnosis of TB in children and, thus, warrants additional investigation. In particular, the diagnostic potential of IFN-γ/MCP-1 ratios should be further explored in larger pediatric cohorts.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>39271436</pmid><doi>10.1016/j.jmii.2024.07.011</doi><tpages>10</tpages><orcidid>https://orcid.org/0009-0006-4497-0318</orcidid><orcidid>https://orcid.org/0000-0002-4125-0423</orcidid><orcidid>https://orcid.org/0000-0003-3717-5384</orcidid><orcidid>https://orcid.org/0000-0003-1986-9016</orcidid><orcidid>https://orcid.org/0000-0001-9618-5027</orcidid><orcidid>https://orcid.org/0000-0002-9560-9104</orcidid><orcidid>https://orcid.org/0000-0002-0982-1636</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1684-1182 |
| ispartof | Journal of microbiology, immunology and infection, 2024-12, Vol.57 (6), p.937-946 |
| issn | 1684-1182 1995-9133 1995-9133 |
| language | eng |
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| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | Adolescent Biomarkers Biomarkers - blood Chemokine CCL2 - blood Child Child, Preschool Cytokines - blood Diagnosis Female Humans Infant Inflammation - blood Interferon-gamma - blood Interleukin-2 - blood Interleukins - blood Latent Tuberculosis - blood Latent Tuberculosis - diagnosis Male Mycobacterium tuberculosis Pediatrics Sensitivity and Specificity Tuberculosis Tuberculosis - blood Tuberculosis - diagnosis |
| title | Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB |
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