ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2017
Involvement of methylated HBHA expressed from Mycobacterium smegmatis in an IFN-γ release assay to aid discrimination between latent infection and active tuberculosis in BCG-vaccinated populations.
Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.
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Who cites it
7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.
- Diagnostic performance of biomarkers for differentiating active tuberculosis from latent tuberculosis: a systematic review and Bayesian network meta-analysis.Frontiers in microbiology · 2024Pooled it
- Pooled it
- 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.Journal of clinical microbiology · 2022Article
- Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study.Frontiers in immunology · 2020Article
- Diagnostic Value of Recombinant Heparin-binding Hemagglutinin Adhesin Protein in Spinal Tuberculosis.Open medicine (Warsaw, Poland) · 2020Article
- A structural overview of mycobacterial adhesins: Key biomarkers for diagnostics and therapeutics.Protein science : a publication of the Protein Society · 2018Review
- Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis (M. tb) infection. However, IGRAs with these antigens cannot discriminate between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin (HBHA) induces relatively high IFN-γ responses in LTBI individuals and low responses in ATB patients, but purification of the native methylated HBHA from cultures of M. tb for immunological tests is complex and time-consuming. To overcome these cumbersome procedures, we constructed a recombinant Mycobacterium smegmatis strain that over-expressed HBHA under control of a strong furA promoter. The methylated activity of purified protein was verified by hybridization with anti-methylated Lys antibody, and the methylated HBHA (mHBHA) was further evaluated for antigen-specific IFN-γ responses in BCG-vaccinated Chinese population. A total of 138 individuals including 86 active TB (ATB) patients, 15 latent TB infection (LTBI) cases, and 37 healthy controls (HC) were tested by using an IFN-γ enzyme-linked immunospot (ELISPOT) assay. The results showed that T-cell responses against mHBHA were always lower in ATB patients than in LTBI individuals, regardless of the site of infection or the results of bacteriological tests. This allowed for a good discrimination between these two groups of M. tb-infected individuals, even in the BCG-vaccinated and high TB-incidence setting that is China. Additionally, combination of mHBHA and RD1 antigens in an IFN-γ release assay enhanced diagnostic efficacy for active TB cases. Taken together, inclusion of the immune response to mHBHA can discriminate healthy LTBI cases from ATB patients.
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