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.

The Journal of Infection
|December 5, 2020
PubMed

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.
Abstract

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