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

J Infect. 2014 Dec;69(6):581-9. doi: 10.1016/j.jinf.2014.05.014. Epub 2014 Jun 23.


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.

Keywords: Ig classes; Latent Mycobacterium tuberculosis infection; Serology; Tuberculosis; Tuberculosis endemic setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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