Added Value of Long-Term Cytokine Release Assays to Detect Mycobacterium tuberculosis Infection in HIV-Infected Subjects in Uganda

作者：Dirix Violette; Schepers Kinda; Massinga Loembe Marguerite; Worodria William; Colebunders Robert; Singh Mahavir; Locht Camille; Kestens Luc; Mascart Francoise^*

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2016, 72(3): 344-352.

DOI：10.1097/qai.0000000000000980

• human
• human immunodeficiency virus
• Mycobacterium tuberculosis
• interferon-gamma release assay
• tuberculosis-associated immune reconstitution inflammatory syndrome
• latent tuberculosis
• cytokines/chemokines

Objectives: To investigate whether mycobacterial antigen-induced cytokine secretions are helpful in detecting Mycobacterium tuberculosis (Mtb) infection in a cohort of HIV-infected patients living in a country with a high burden of Mtb and HIV infections, and to determine their predictive value for the development of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome.
Design: A total of 352 HIV-infected patients (186 with active TB) were prospectively enrolled when initiating antiretroviral therapy (ART). Sequential blood samples were collected during the first 6 months of ART. Eighty-three HIV-uninfected subjects (39 with active TB) were enrolled as controls.
Methods: The concentrations of 13 cytokines were measured in supernatants from blood mononuclear cells in vitro stimulated with purified protein derivative (PPD), heparin-binding hemagglutinin (HBHA) or early secreted antigen-6 (ESAT-6) and culture filtrate protein-10 (CFP-10), and results were compared with those of tuberculin skin tests (TST).
Results: The best detection of Mtb infection was achieved by ESAT-6/CFP-10-induced interferon-gamma concentrations, but results were often negative for patients with CD4(+) T-cell counts <50 per cubic millimeters. Patients with active TB were identified by high ESAT-6/CFP-10-induced interleukin-6. Conversions of interferon-gamma-release assays (IGRA) and TST occurred under ART, and combined TB and antiretroviral treatments of coinfected patients resulted in a decrease of ESAT-6/CFP-10-induced and an increase of HBHA-induced interferon-gamma responses. No Mtb antigen-induced cytokines allowed us to predict TB-immune reconstitution inflammatory syndrome or ART-associated TB.
Conclusions: In Uganda, ESAT-6/CFP-10-IGRA is better in detecting Mtb infection than TST and, when combined with an HBHA-IGRA, could help to evaluate anti-TB treatment success.

• 出版日期2016-7-1