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Mycobacterial heparin-binding haemagglutinin adhesion-induced interferon & antibody for detection of tuberculosis.

ABSTRACT: BACKGROUND & OBJECTIVES: Mycobacterial heparin-binding haemagglutinin adhesin (HBHA) plays an important role in humoral and cellular immune response and is a potential diagnostic tool for tuberculosis (TB) serodiagnosis. This study was carried out to assess the usefulness of HBHA in TB clinics for differential diagnosis of pulmonary and extra-pulmonary TB (PTB, EPTB). METHODS: In this study, 165 outpatients and 133 healthy volunteers were included to investigate the role of HBHA in TB diagnosis including the serodiagnostic tests and the interferon-? release assays (IGRAs). The healthy volunteers were all without BCG vaccination including 73 subjects with purified protein derivative (PPD) (-) and 60 ones with PPD (+) (that is P-B- and P+B-). Of all the 165 outpatients 77 were PTB and 88 were EPTB. HBHA protein was used for serodiagnostic tests and IGRAs in peripheral blood mononuclear cells. RESULTS: HBHA-specific antibody levels in the serum of healthy subjects were significantly different from the patients with PTB or EPTB (P<0.05). HBHA specific antibody levels in PTB patients could differentiate from EPTB with limited sensitivity (77.08%; 95%CI, 62.69 to 87.97%) and specificity (87.50%; 95%CI, 74.75 to 95.27%). IFN-? levels in the healthy (P+B- and P-B-) groups were significantly different (P<0.01) with a detection sensitivity of 84.8% (95%CI, 68.54 to 93.02%) and specificity of 80.7% (95%CI, 65.22 to 92.62%). The PTB and EPTB subjects showed no difference in IFN-? production. INTERPRETATION & CONCLUSIONS: HBHA serodiagnostic test with IGRAs had the limited potential for use as auxiliary tools for the differential diagnosis of PTB and EPTB, since both methods showed low sensitivity and specificity.

SUBMITTER: Sun Z

PROVIDER: S-EPMC3103176 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Mycobacterial heparin-binding haemagglutinin adhesion-induced interferon & antibody for detection of tuberculosis.

Sun Zhaogang Z Nie Lihui L Zhang Xuxia X Li Yan Y Li Chuanyou C

The Indian journal of medical research 20110401

<h4>Background & objectives</h4>Mycobacterial heparin-binding haemagglutinin adhesin (HBHA) plays an important role in humoral and cellular immune response and is a potential diagnostic tool for tuberculosis (TB) serodiagnosis. This study was carried out to assess the usefulness of HBHA in TB clinics for differential diagnosis of pulmonary and extra-pulmonary TB (PTB, EPTB).<h4>Methods</h4>In this study, 165 outpatients and 133 healthy volunteers were included to investigate the role of HBHA in ...[more]

PMID: 21537096

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Project description:BackgroundThe Mycobacterial heparin-binding hemagglutinin (HBHA) is an important latency-associated antigen that can be used to distinguish between latent tuberculosis infection (LTBI) and active tuberculosis (ATB). Although many studies were explored the efficiency of the HBHA-induced interferon-γ release assay (IGRA) in different populations, the clinical differential value of HBHA-IGRA is still controversial. Therefore, the aim of this study was to determine whether the HBHA-IGRA can be used as an efficient test for the discrimination of LTBI and ATB by a systematic review and meta-analysis.MethodsRelevant articles were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library on Oct 18, 2020, with no start date limitation. The quality of each study was evaluated using Review Manager 5.4. The Stata MP v.14.0 software was used to combine sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve, and area under SROC (AUC) to evaluate the diagnostic value of HBHA-IGRA for discrimination of LTBI and ATB. Meta-regression and subgroup analysis were performed for the sources of heterogeneity based on the selection criteria for active TB, the population, the TB burden, the type of antigen, the type of sample, and the time of antigen stimulation.ResultsA total of 13 studies (14 results) were included in this meta-analysis, including 603 ATB patients and 514 LTBI individuals. The pooled sensitivity and specificity of the HBHA-IGRA for discrimination of the LTBI and ATB were 0.70 (95% CI, 0.57~0.80) and 0.78 (95% CI, 0.71~0.84), respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 3.15 (95%CI, 2.43~4.09), 0.39 (95% CI, 0.27~0.56), and 8.11 (95% CI, 4.81~13.67), respectively. The AUC was 0.81 (95% CI, 0.77~0.84). The subgroup analysis showed that the main source of heterogeneity was due to the HIV-infected population incorporated, and the different selection criteria of active TB subjects would also lead to the variation of the pooled sensitivity and specificity. Different TB burdens, HBHA antigen types, sample types, antigen stimulation time and BCG vaccination did not affect the heterogeneity in this analysis.ConclusionThe HBHA-IGRA is a promising immunodiagnostic test for discrimination of latent and active TB, which can be added in commercial IGRAs to enhance the differential diagnostic performance.

Project description:BackgroundTuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment.MethodsThis multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA.FindingsBetween December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p < 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (<14%) or high neutrophil percentages (>79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70-80%) but not their specificity (<30%).ConclusionWe showed that QFT-P and rmsHBHA IFN-γ responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN-γ discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.

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Mycobacterial heparin-binding haemagglutinin adhesion-induced interferon & antibody for detection of tuberculosis.

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Mycobacterial heparin-binding haemagglutinin adhesion-induced interferon & antibody for detection of tuberculosis.

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