A new potential biomarker for childhood tuberculosis

Thomas, Tania A; Brighenti, Susanna; Andersson, Jan; Sack, David A.; Raqib, Rubhana

doi:10.1136/thx.2010.147363

Cited by 14 publications

(13 citation statements)

References 5 publications

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“…These declines were most pronounced among those confirmed to have drug-sensitive TB, which suggests that potent anti-TB therapy may be associated with reduced TB antigenic stimulation. These trends are similar to those previously demonstrated among adults and children [10, 17]. During the time interval tested in our protocol, the reductions in ALS responses were not associated with treatment outcome.…”

Section: Discussionsupporting

confidence: 90%

“…For TB, the ALS assay captures the spontaneous release of anti-mycobacterial IgG antibodies from peripheral blood and has been used for the diagnosis of active TB and treatment monitoring [4, 9, 10]. Although this is an antibody-based assay, it differs from traditional serologic tests by discarding the serum and measuring incident antibody production directly from the lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Antibody in Lymphocyte Supernatant Assay to Detect Active Tuberculosis

Sariko¹,

Anderson²,

Mujaga³

et al. 2017

PLoS ONE

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BackgroundWe aimed to evaluate the antibody in lymphocyte supernatant (ALS) assay as a biomarker to diagnose tuberculosis among adults from Tanzania with and without HIV.MethodsAdults admitted with suspicion for tuberculosis had sputa obtained for GeneXpert MTB/RIF, acid-fast bacilli smear and mycobacterial culture; blood was obtained prior to treatment initiation and after 4 weeks. Adults hospitalized with non-infectious conditions served as controls. Peripheral blood mononuclear cells were cultured unstimulated for 72 hours. Anti-mycobacterial antibodies were measured from culture supernatants by ELISA, using BCG vaccine as the coating antigen. Median ALS responses were compared between cases and controls at baseline and between cases over time.ResultsOf 97 TB cases, 85 were microbiologically confirmed and 12 were clinically diagnosed. Median ALS responses from TB cases (0.366 OD from confirmed cases and 0.285 from clinical cases) were higher compared to controls (0.085, p<0.001). ALS responses did not differ based on HIV status, CD4 count or sputum smear status. Over time, the median ALS values declined significantly (0.357 at baseline; 0.198 after 4-weeks, p<0.001).ConclusionsRobust ALS responses were mounted by patients with TB regardless of HIV status, CD4 count, or low sputum bacillary burden, potentially conferring a unique niche for this immunologic biomarker for TB.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Evaluation of the Antibody in Lymphocyte Supernatant Assay to Detect Active Tuberculosis

Sariko¹,

Anderson²,

Mujaga³

et al. 2017

PLoS ONE

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“…Importantly, it has been shown that BCG-specific IgG titres gradually decrease after 2 and 6 months of successful anti-TB therapy, but remain high in patients infected with drug-resistant TB, also indicating that high levels of ASCs are maintained during progressive TB 46 7 …”

Section: Discussionmentioning

confidence: 99%

“…This method detects antigen-specific antibodies secreted by peripheral blood mononuclear cells (PBMCs) and has also been used to assess mucosal immune responses to oral cholera8 and typhoid9 vaccines, and in patients with enterotoxigenic Escherichia coli (ETEC) diarrhoea 10. In contrast to conventional serology,11 12 which involves assessment of stable serum antibodies,7 the ALS test is based on the spontaneous release of BCG-specific IgG antibodies from peripheral plasmablasts temporarily present in the blood 3–5. Our hypothesis is that pathogen-specific antibody secreting cells (ASCs) are only present in blood during active or subclinical disease13 14 and not during latent infection or under healthy conditions 15.…”

Section: Introductionmentioning

confidence: 99%

BCG-specific IgG-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in HIV negative and HIV positive patients

Ashenafi

Aderaye

Zewdie

et al. 2012

Thorax

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BackgroundDiagnosis of active tuberculosis (TB) among sputum-negative cases, patients with HIV infection and extra-pulmonary TB is difficult. In this study, assessment of BCG-specific IgG-secreting peripheral plasmablasts, was used to identify active TB in these high-risk groups.MethodsPeripheral blood mononuclear cells were isolated from patients with TB and controls and cultured in vitro using an assay called Antibodies in Lymphocyte Supernatant, which measures spontaneous IgG antibody release from migratory plasmablasts. A BCG-specific ELISA and flow cytometry were used to quantify in vivo activated plasmablasts in blood samples from Ethiopian subjects who were HIV negative or HIV positive. Patients diagnosed with different clinical forms of sputum-negative active TB or other diseases (n=96) were compared with asymptomatic individuals including latent TB and non-TB controls (n=85). Immunodiagnosis of TB also included the tuberculin skin test and the interferon (IFN)-γ release assay, QuantiFERON.ResultsThis study demonstrated that circulating IgG+ plasmablasts and spontaneous secretion of BCG-specific IgG antibodies were significantly higher in patients with active TB compared with latent TB cases and non-TB controls. BCG-specific IgG titres were particularly high among patients coinfected with TB and HIV with CD4 T-cell counts <200 cells/ml who produced low levels of Mycobacterium tuberculosis-specific IFNγ in vitro.ConclusionsThese results suggest that BCG-specific IgG-secreting peripheral plasmablasts could be successfully used as a host-specific biomarker to improve diagnosis of active TB, particularly in people who are HIV positive, and facilitate administration of effective treatment to patients. Elevated IgG responses were associated with impaired peripheral T-cell responses, including reduced T-cell numbers and low M tuberculosis-specific IFNγ production.

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“…It showed promising results as a biomarker for active TB in both adults9 10 and children 11 12. In this issue of Thorax , Ashenafi et al evaluated this assay in parallel with the tuberculin skin test (TST) and an IGRA (Quantiferon TB-Gold-in-tube) in adult TB patients (with and without HIV to coinfection) and asymptomatic controls with and without LTBI in Ethiopia.…”

mentioning

confidence: 99%

Tuberculosis immunodiagnosis: delving below the surface

Lalvani

Connell

2013

Thorax

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It is one hundred and thirty years since Franz Ziehl and Friedrich Neelsen developed the rapid stain for acid-fast bacilli; 1 2 accurate point-of-care diagnosis of active tuberculosis (TB) remains a major unmet clinical need. With the sensitivity of the Ziehl-Neelsen stain in sputum less than 50% and more than 20% of TB cases negative on both acid-fast stain and culture for Mycobacterium tuberculosis, there has long been a yawning gap in the diagnostic toolkit for TB. New rapid molecular methods have recently improved detection of M tuberculosis nucleic acids in sputum providing diagnostic sensitivity that is much higher than sputum-smear microscopy but lower than culture.3

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A new potential biomarker for childhood tuberculosis

Cited by 14 publications

References 5 publications

Evaluation of the Antibody in Lymphocyte Supernatant Assay to Detect Active Tuberculosis

Evaluation of the Antibody in Lymphocyte Supernatant Assay to Detect Active Tuberculosis

BCG-specific IgG-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in HIV negative and HIV positive patients

Tuberculosis immunodiagnosis: delving below the surface

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