title: Serologic diagnosis of tuberculosis by combining Ig classes against selected mycobacterial targets.
abstract: BACKGROUND
  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: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa; Lionex Diagnostics and Therapeutics, 38126 Braunschweig, Germany.
authors: Ralf
authors: R
authors: Baumann
authors: Lionex Diagnostics and Therapeutics, 38126 Braunschweig, Germany.
authors: Susanne
authors: S
authors: Kaempfer
authors: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa.
authors: Novel N
authors: NN
authors: Chegou
authors: Lionex Diagnostics and Therapeutics, 38126 Braunschweig, Germany.
authors: Wulf
authors: W
authors: Oehlmann
authors: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa.
authors: André G
authors: AG
authors: Loxton
authors: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors: Stefan H E
authors: SH
authors: Kaufmann
authors: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa.
authors: Paul D
authors: PD
authors: van Helden
authors: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa.
authors: Gillian F
authors: GF
authors: Black
authors: Lionex Diagnostics and Therapeutics, 38126 Braunschweig, Germany. Electronic address: info@lionex.de.
authors: Mahavir
authors: M
authors: Singh
authors: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa.
authors: Gerhard
authors: G
authors: Walzl
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D000942:Antigens, Bacterial / Q000097:blood; D016022:Case-Control Studies; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; C050016:lipoarabinomannan; C072681:Mycobacterium tuberculosis antigens
keywords: Ig classes; Latent Mycobacterium tuberculosis infection; Serology; Tuberculosis; Tuberculosis endemic setting