Optimal Detection of Latent Mycobacterium tuberculosis Infection by Combined Heparin-Binding Hemagglutinin (HBHA) and Early Secreted Antigenic Target 6 (ESAT-6) Whole-Blood Interferon Gamma Release Assays

Dirix, Violette; Dauby, Nicolás; Hites, Maya; Watelet, E.; Praet, Anne Van; Godefroid, Audrey; Petit, Emmanuelle; Singh, Mahavir; Locht, Camille; Mascart, Françoise; Corbière, Véronique

doi:10.1128/jcm.02443-21

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…It is of note that, except for one patient, mediastinal TBLA was characterized by very high IFN-γ responses to ESAT-6, associated to positive responses to HBHA, albeit lower than those to ESAT-6 ( Table 4 ). Such IGRA profiles were previously reported to be highly suggestive of active TB, whereas the reverse profile (high response to HBHA with low or absent response to ESAT-6) is suggestive of LTBI [ 7 , 8 , 9 , 10 , 11 , 13 , 14 , 15 ]. Finally, the HBHA/ESAT-6 IGRA was positive for the three patients with disseminated TBLA (group 3) with a profile highly suggestive of active TB ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 91%

“…IGRA results were strongly positive for the six patients with TBLA, with isolated IFN-γ secretion to ESAT-6 for one of them (patient n°7) and higher IFN-γ secretion in response to ESAT-6 than to HBHA for two others (patients n°3 and n°6) ( Table 4 and Figure 1 ). These IGRA profiles, which are highly suggestive of active TB [ 7 , 9 , 11 , 13 ], characterized patients with a unilateral cervical ADP (n°3), a miliary TB (n°6), and bilateral cervical ADPs with axillar ADP (n°7). The other patients with unilateral cervical ADP had lower IFN-γ secretion in response to ESAT-6 than to HBHA, a profile characteristic of patients who better control M. tuberculosis infection [ 9 , 14 , 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…Consequently, they cannot be used to differentiate TBLA from LTBI subjects potentially suffering from sarcoidosis or lymphoma [ 6 ]. In contrast, IGRA using two different stage-specific mycobacterial antigens, heparin-binding haemagglutinin (HBHA) and early-secreted antigenic target-6 (ESAT-6), are able to differentiate LTBI from active TB [ 7 , 8 , 9 , 10 , 11 ]. Therefore, we retrospectively evaluated here the potential of this combined HBHA/ESAT-6 IGRA for the diagnosis of TBLA.…”

Section: Introductionmentioning

confidence: 99%

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

Mascart

Hites

Watelet

et al. 2023

JCM

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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.

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Section: Discussionmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Mascart

Hites

Watelet

et al. 2023

JCM

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“…An HBHA-IGRA is an already well-known promising immunodiagnostic test, mainly designed for the detection of TB infection status and its differential diagnosis from PTB ( 10 , 14 , 19 , 21 ). HBHA is a surface-associated protein involved in adherence to epithelial cells, which has been shown to be required for extrapulmonary dissemination of Mtb ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have demonstrated the potential value of HBHA-IGRA as a biomarker to distinguish TB infection from pulmonary TB (PTB) ( 19 – 21 ). However, these studies have mainly focused on PTB.…”

Section: Introductionmentioning

confidence: 99%

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

Bchiri,

Bouzekri,

Ouni

et al. 2023

Microbiol Spectr

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Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is a serious health problem in Tunisia. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis (CNTL). Here, we evaluated the performance of heparin-binding hemagglutinin (HBHA) interferon-gamma (IFN-γ) release assay (IGRA) for the diagnosis of CTL. In addition, we evaluated granzyme B, granulysin, and perforin release assays as CTL biomarkers and assessed their potential contribution to improve HBHA-IGRA performance. Peripheral blood mononuclear cells from CTL-suspected patients were stimulated with HBHA, early secreted antigenic target 6 (ESAT-6), or purified protein derivative (PPD) for 24 h in the presence of IL-7. Cytotoxic mediators and IFN-γ release were assessed by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were used to evaluate the capacity of HBHA, ESAT-6, and PPD to discriminate between CTL ( n = 27) and CNTL ( n = 21). After applying bivariate and multivariate analyses, IFN-γ responses to HBHA appeared to offer the best distinction between CTL and CNTL, with an area under the curve of 0.9947, associated with 95.24% and 100% sensitivity and specificity, respectively. A principal component analysis showed clear clustering of the CTL versus the CNTL groups. This clustering was mainly attributed to HBHA-induced IFN-γ, PPD-induced granzyme B, and PPD-induced IFN-γ. These results thus suggest that the HBHA-IGRA provides high diagnostic accuracy for CTL versus CNTL, with high sensitivity and specificity. Combining HBHA-induced IFN-γ and PPD-induced granzyme B improves the accuracy to identify CTL. IMPORTANCE Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is currently a major health problem in Tunisia and in several regions around the world. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis. This study demonstrates the added value of the heparin-binding hemagglutinin-interferon-gamma release assay as an immunoassay in the context of CTL.

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Mycobacterium tuberculosis: The Mechanism of Pathogenicity, Immune Responses, and Diagnostic Challenges

Mohammadnabi,

Shamseddin,

Emadi

et al. 2024

Clinical Laboratory Analysis

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BackgroundThe infection caused by Mycobacterium tuberculosis arises from a complex interplay between the host immune system and the bacteria. Early and effective treatment of this disease is of great importance in order to prevent the emergence of drug‐resistant strains. This necessitates the availability of fast and reliable diagnostic methods for managing affected cases. One reason why this study is significant is the lack of a comprehensive review in this field that thoroughly examines the importance, pathogenesis, and diagnosis of M. tuberculosis. Therefore, the aim of this review is to provide updated information on M. tuberculosis.MethodsWe investigate the virulence factors, pathogenicity, and diagnostic methods of this bacterium, alongside the clinical symptoms and interpretation of different types of tuberculosis, including cerebral, miliary, nerve, and tubercular tuberculosis.ResultsMycobacterium tuberculosis acts as the causative agent of human tuberculosis and is regarded as one of the most adaptable human pathogens. M. tuberculosis possesses several virulence factors that help the bacterium evade mucous barriers. The rise of multidrug‐resistant tuberculosis (MDR‐TB) in both developing and industrialized countries emphasizes the need for rapid diagnostic methods.ConclusionsNon‐protein virulence factors play a crucial role in the pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). The bacterial cell membrane contains proteins that modulate the host immune response. For instance, ESAT‐6, either alone or in combination with CFP‐10, reduces immune activity. While molecular techniques—such as DNA microarray, luciferase reporter assay, polymerase chain reaction (PCR), DNA and RNA probes, next‐generation sequencing, and whole‐genome sequencing—offer rapid, sensitive, and specific detection of M. tuberculosis, these methods are expensive and require technical expertise.

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Optimal Detection of Latent Mycobacterium tuberculosis Infection by Combined Heparin-Binding Hemagglutinin (HBHA) and Early Secreted Antigenic Target 6 (ESAT-6) Whole-Blood Interferon Gamma Release Assays

Cited by 7 publications

References 29 publications

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

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

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

Mycobacterium tuberculosis: The Mechanism of Pathogenicity, Immune Responses, and Diagnostic Challenges

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