Tuberculosis immunodiagnosis: delving below the surface

Lalvani, Ajit; Connell, David

doi:10.1136/thoraxjnl-2012-202481

Cited by 3 publications

(3 citation statements)

References 16 publications

(14 reference statements)

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“…These supernatants were harvested from undiluted whole blood following overnight culture. This could be sufficient time to allow secretion of antibodies into supernatants by M.tb specific antibody secreting cells [ 33 ] and could consequently affect antibody concentration. However, there was no difference in the concentrations of antibodies to the DosR proteins between APTB cases for which only QFT nil control supernatants were tested and uninfected individuals for which serum samples were used, in the adjusted analysis.…”

Section: Discussionmentioning

confidence: 99%

Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection

Kimuda

Nalwoga

Levin

et al. 2017

Journal of Immunology Research

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Latent tuberculosis infection (LTBI) is evidence of immunological control of tuberculosis. Dormancy survival regulator (DosR) regulon-encoded proteins may have a role in the maintenance of LTBI. T cell responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were found to be most frequent among household contacts of TB cases from Uganda compared to other DosR proteins, but antibody responses were not described. We characterized antibody responses to these proteins in individuals from Uganda. Antibodies to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins were measured in 68 uninfected individuals, 62 with LTBI, and 107 with active pulmonary tuberculosis (APTB) cases. There were no differences in the concentrations of antibodies to Rv0081, Rv1735c, and Rv1737c DosR regulon-encoded proteins between individuals with LTBI and APTB and those who were uninfected. LTBI was associated with higher concentrations of antibodies to Rv1733c in female participants [adjusted geometric mean ratio: 1.812, 95% confidence interval (CI): 1.105 2.973, and p = 0.019] but not in males (p value for interaction = 0.060). Antibodies to the four DosR regulon-encoded proteins investigated may not serve as good biomarkers of LTBI in the general population. More of the M.tb proteome needs to be screened to identify proteins that induce strong antibody responses in LTBI.

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Section: Discussionmentioning

confidence: 99%

Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection

Kimuda

Nalwoga

Levin

et al. 2017

Journal of Immunology Research

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“…This result may therefore reflect the low levels of circulating antibody secreting cells in individuals without an active infection [ 24 ]. Studies measuring antibodies in lymphocyte supernatant assays suggest that there are higher levels of anti-mycobacterial antibodies following culture of cells from active TB cases [ 14 ]. However, we were not able to access matched serum and QFT-GIT supernatant pairs from active TB cases to investigate this effect in whole blood culture supernatants.…”

Section: 0 Discussionmentioning

confidence: 99%

“…However, it remains unknown whether the concentrations of antibodies in QFT-GIT supernatants are also representative of circulating antibody. Since QFT-GIT supernatants are obtained from 16–24 h whole blood cultures it is possible that this period of culture could be sufficient for the production of antibodies into supernatant by antibody secreting cells that may be present in circulation [ 13 , 14 ]. Additionally, stimulation by antigens in test or mitogen control tubes could lead to the differentiation of memory B cells into antibody secreting cells [ 15 , 16 ], leading to a higher concentration of antibodies in QFT-GIT supernatants compared to sera.…”

Section: 0 Introductionmentioning

confidence: 99%

Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses

et al. 2017

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QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.

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Biomarkers of Tuberculosis: A Research Roadmap

2013

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Tuberculosis (TB) continues to represent a major public health problem worldwide. Prompt and accurate diagnosis and effective treatment are fundamental to reducing morbidity and mortality and curtailing spread of infection. Furthermore, tackling the large reservoir of latent infection is the cornerstone to TB control in many high income low TB incidence countries. However, our existing toolkit for prevention, diagnosis and treatment remains outdated and inadequate. Here, we discuss the key targets for biomarker research and discovery in TB and recent developments in the field. We focus on host biomarkers, in particular: correlates of vaccine efficacy and sterilizing immunity; biomarkers of latent TB infection, including diagnosis, risk of progression to active TB and response to treatment; and markers of active TB, including diagnosis, response to treatment and risk of relapse. Recent scientific and technological advances have contributed to significant recent progression in biomarker discovery. Although there are clear remaining paucities, continued efforts within scientific, translational and clinical studies are likely to yield a number of clinically useful biomarkers of TB in the foreseeable future.

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Tuberculosis immunodiagnosis: delving below the surface

Cited by 3 publications

References 16 publications

Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection

Humoral Responses to Rv1733c, Rv0081, Rv1735c, and Rv1737c DosR Regulon-Encoded Proteins of Mycobacterium tuberculosis in Individuals with Latent Tuberculosis Infection

Use of QuantiFERON®-TB Gold in-tube culture supernatants for measurement of antibody responses

Biomarkers of Tuberculosis: A Research Roadmap

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