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Host cytokine responses induced after overnight stimulation with novel M. tuberculosis infection phase-dependent antigens show promise as diagnostic candidates for TB disease.
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- Author(s): Essone PN;Essone PN; Chegou NN; Chegou NN; Loxton AG; Loxton AG; Stanley K; Stanley K; Kriel M; Kriel M; van der Spuy G; van der Spuy G; Franken KL; Franken KL; Ottenhoff TH; Ottenhoff TH; Walzl G; Walzl G
- Source:
PloS one [PLoS One] 2014 Jul 15; Vol. 9 (7), pp. e102584. Date of Electronic Publication: 2014 Jul 15 (Print Publication: 2014).- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- Publication Information: Original Publication: San Francisco, CA : Public Library of Science
- Subject Terms: Cytokines/*blood ; Mycobacterium tuberculosis/*immunology ; Tuberculosis, Pulmonary/*blood; Adolescent ; Adult ; Antigens, Bacterial/immunology ; Biomarkers/blood ; Female ; Humans ; Interferon-gamma Release Tests ; Male ; Pilot Projects ; ROC Curve ; Tuberculosis, Pulmonary/diagnosis ; Tuberculosis, Pulmonary/immunology ; Young Adult
- Abstract: Background: We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants.
Methods: We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform.
Results: The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72-84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation.
Conclusion: Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies. - References: Clin Vaccine Immunol. 2011 Apr;18(4):676-83. (PMID: 21248154)
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Tuberculosis (Edinb). 2012 Mar;92(2):148-59. (PMID: 22226907) - Accession Number: 0 (Antigens, Bacterial)
0 (Biomarkers)
0 (Cytokines) - Publication Date: Date Created: 20140716 Date Completed: 20151014 Latest Revision: 20211021
- Publication Date: 20240104
- Accession Number: PMC4099213
- Accession Number: 10.1371/journal.pone.0102584
- Accession Number: 25025278
- Source:
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