Analysis of a Combined HBHA and ESAT-6-Interferon-γ-Release Assay for the Diagnosis of Tuberculous Lymphadenopathies

Abstract

Background and Objectives: The incidence of tuberculosis lymphadenopathy (TBLA) is increasing, and diagnostic procedures lack sensitivity and are often highly invasive. TBLA may be asymptomatic, and differential diagnosis with other adenopathies (ADPs) is difficult. We evaluated a blood-cell interferon-γ release assay (IGRA) with two different stage-specific mycobacterial antigens for the differential diagnosis of ADP suspected of mycobacterial origin. Methods: Twenty-one patients were included and divided into three groups: (1) cervical/axillar ADP (n = 8), (2) mediastinal ADP (n = 10), and (3) disseminated ADP (n = 3). The mycobacterial antigens used for the IGRA were the heparin-binding haemagglutinin (HBHA) and the early-secreted antigenic target-6 (ESAT-6), a latency-associated antigen and a bacterial replication-related antigen, respectively. Diagnosis of TBLA based on microbiological results and/or response to anti-TB treatment was obtained for 15 patients. Results: An IGRA profile highly suggestive of active TB (higher IFN-γ response to ESAT-6 compared to HBHA) was found for 3/6 TBLA patients from group 1, and for all the TBLA patients from groups 2 and 3, whereas this profile was not noticed in patients with a final alternative diagnosis. Conclusion: These results highlight the potential value of this combined HBHA/ESAT-6 IGRA as a triage test for the differential diagnosis of ADP.

HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis

“…Even if this suggests that HBHA may allow a better distinction between the studied groups than the other two Ags, these results may be due to the immune profile of the CNTL with TB infection. Our results are, however, in line with those recently reported in isolated CTL from patients living in a low TB-incidence country ( 28 ).…”

“…However, even though limited information is available, blood immune-based diagnosis may be different for EPTB compared to PTB. In contrast to PTB characterized most often by low HBHA-induced IFN-γ concentrations among PBMCs, HBHA may induce higher IFN-γ concentration secretion in patients with EPTB ( 28 and L. Aerts, personal communication). Thus, HBHA-blood-based tests may offer in some cases a valuable tool for diagnosis, particularly in cases where the infection is located in tissues outside the lungs, when traditional diagnostic strategies, such as sputum-based tests, may not be effective.…”

“…Many studies focused on the utility of the use of tests based on HBHA for TB infection in subjects from different countries and at different ages including children, and in peripheral blood and at the lung site ( 24 – 27 ). To the best of our knowledge, no study has yet assessed the utility of HBHA-IGRA for the diagnosis of CTL, except in the recent study by Mascart et al ( 28 ).…”