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An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
Interleukin-6 and Mycobacterium tuberculosis dormancy antigens improve diagnosis of tuberculosis
Ernest Adankwah1, Norman Nausch1, Difery Minadzi2
1Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Medical Faculty Heinrich-Heine University, Moorenstr. 5, 40225 Duesseldorf, Germany.
Insights
Interferon-gamma release assays (IGRAs) for tuberculosis diagnosis can be improved using alternative cytokines like IL-6 and latency antigens. This approach enhances the detection and classification of Mycobacterium tuberculosis infection in patients and contacts.
Area of Science:
- Immunology
- Infectious Diseases
- Biomarker Discovery
Background:
- Interferon-gamma release assays (IGRAs) are crucial for diagnosing Mycobacterium tuberculosis infection but have limitations in sensitivity.
- Exploring alternative cytokines and latency-associated antigens could enhance the accuracy of immune-based tuberculosis detection.
Purpose of the Study:
- To evaluate the potential of alternative cytokines and M. tuberculosis latency-associated antigens to improve the diagnosis of tuberculosis.
- To compare the diagnostic performance of these novel markers against traditional IGRA methods.
Main Methods:
- Multiplex cytokine analysis was performed on culture supernatants after in vitro restimulation with M. tuberculosis IGRA and latency-associated antigens (Rv2628, Rv1733).
- The study included tuberculosis patients (n=22) and asymptomatic contacts (ACs) (n=20) from Ghana.
Main Results:
- Four cytokines (IFNγ, IP-10, IL-22, IL-6) increased significantly post-restimulation. IL-6 was significantly higher in tuberculosis patients.
- IL-6 demonstrated the highest sensitivity (91% for patients, 85% for ACs) compared to IFNγ, IP-10, and IL-22.
- A combination of Rv2628/Rv1733-induced IFNγ and IGRA-antigen-induced IL-6 optimally classified tuberculosis patients and ACs (AUC: 0.92).
Conclusions:
- Alternative cytokines, particularly IL-6, and latency-associated antigens Rv1733/Rv2628 show promise for improving M. tuberculosis detection.
- These markers can effectively classify individuals with tuberculosis infection and asymptomatic contacts, offering a potential advancement in diagnostic strategies.
Objectives:
IFNγ-release assays (IGRAs) used for diagnosis of Mycobacterium (M.) tuberculosis infection have limited sensitivity. Alternative cytokines and M. tuberculosis latency-associated antigens may improve immune-based tests.
Methods:
Multiplex cytokine analyses was done in culture supernatants after 6-day in vitro restimulation with M. tuberculosis IGRA and latency-associated antigens (i.e. Rv2628, Rv1733) in tuberculosis patients (n = 22) and asymptomatic contacts (AC)s (n = 20) from Ghana.
Results:
Four cytokines (i.e. IFNγ, IP-10, IL-22 and IL-6) were significantly increased after IGRA-antigen specific restimulation. IFNγ, IP-10, and IL-22 correlated positively and showed no differences between the study groups whereas IGRA-antigen induced IL-6 was significantly higher in tuberculosis patients. Using adjusted IGRA criteria, IL-6 showed the highest sensitivity for detection of tuberculosis patients (91%) and ACs (85%) as compared to IFNγ, IP-10, and IL-22. Rv2628 and Rv1733 restimulation induced significantly higher IFNγ, IP-10, and IL-22 concentrations in ACs. Combined antigen/cytokine analyses identified study group specific patterns and a combination of Rv2628/Rv1733 induced IFNγ with IGRA-antigen induced IL-6 was optimal for classification of tuberculosis patients and ACs (AUC: 0.92, p<0.0001).
Conclusions:
We demonstrate the potency of alternative cytokines, especially IL-6, and latency-associated antigens Rv1733/Rv2628 to improve detection of M. tuberculosis infection and to classify tuberculosis patients and healthy contacts.
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