Serologic diagnosis of tuberculosis by combining Ig classes against selected mycobacterial targets.

Abstract

INTRODUCTION:

Accurate, simple and cost-effective diagnostic tests are needed for diagnosis of active tuberculosis (TB). Serodiagnosis is attractive as it can be harnessed for point-of-care tests.

METHODS:

We evaluated, in a blinded fashion, the sensitivity and specificity of serologic immunoglobulin (Ig)G, IgA and/or IgM responses to Apa, heat shock protein (HSP) 16.3, HSP20, PE35, probable thiol peroxidase Tpx and lipoarabinomannan (LAM) in 42 HIV-negative South African pulmonary TB patients and 67 control individuals. The status of latent Mycobacterium tuberculosis infection (LTBI) among controls was defined through the TST and IFN-γ release assays (IGRAs). We evaluated 47 definite LTBI (IGRA(+)/LTBI), 8 putative LTBI (IGRA(-)/TST(+)) and 12 TB-uninfected (non-LTBI) subjects.

RESULTS:

In contrast to anti-PE35 IgA, anti-PE35 IgG and particularly anti-Apa IgA, performances of anti-LAM IgG and selected anti-protein antibodies were less affected by inclusion of LTBI participants into the analysis. Anti-LAM IgG showed with a sensitivity/specificity of 71.4%/86.6% (p < 0.001) the best discrimination between TB and non-TB subjects. Selected five-antibody-combinations (including anti-LAM IgG, anti-LAM IgA and anti-Tpx IgG) further improved this performance to an accuracy exceeding 86%.

CONCLUSIONS:

Antibody responses to some Mycobacterium tuberculosis antigens often also reflect latent infection explaining the poor performance of antibody-based tests for active TB in TB-endemic settings. Our results suggest that rather a combination of serological responses against selected protein and non-protein antigens and different Ig classes should be investigated for TB serodiagnostics.

• Authors: Ralf Baumann, Susanne Kaempfer, Novel N Chegou, Wulf Oehlmann, André G Loxton, Stefan H E Kaufmann, Paul D van Helden, Gillian F Black, Mahavir Singh, Gerhard Walzl
• Journal: The Journal of infection (J Infect) Vol. 69 Issue 6 Pg. 581-9 (Dec 2014) ISSN: 1532-2742 [Electronic] England
• PMID: 24968240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Immunoglobulin Isotypes
• Lipopolysaccharides
• lipoarabinomannan
• Mycobacterium tuberculosis antigens

Topics

• Adolescent
• Adult
• Antibodies, Bacterial (blood, immunology)
• Antigens, Bacterial (blood)
• Case-Control Studies
• Cloning, Molecular
• Female
• Humans
• Immunoglobulin Isotypes (blood)
• Latent Tuberculosis (diagnosis)
• Lipopolysaccharides (blood, immunology)
• Male
• Middle Aged
• Multivariate Analysis
• Sensitivity and Specificity
• Serologic Tests
• Tuberculosis, Pulmonary (diagnosis)
• Young Adult