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

• Published in: The Journal of infection Vol. 69; no. 6; pp. 581 - 589
• Main Authors: Baumann, Ralf, Kaempfer, Susanne, Chegou, Novel N, Oehlmann, Wulf, Loxton, André G, Kaufmann, Stefan H.E, van Helden, Paul D, Black, Gillian F, Singh, Mahavir, Walzl, Gerhard
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-12-2014; Elsevier
• Subjects: Adolescent; Adult; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens, Bacterial - blood; Bacterial diseases; Biological and medical sciences; Case-Control Studies; Cloning, Molecular; Female; General aspects; Human bacterial diseases; Human immunodeficiency virus; Humans; Ig classes; Immunoglobulin Isotypes - blood; Infectious Disease; Infectious diseases; Latent Mycobacterium tuberculosis infection; Latent Tuberculosis - diagnosis; Lipopolysaccharides - blood; Lipopolysaccharides - immunology; Male; Medical sciences; Middle Aged; Multivariate Analysis; Mycobacterium tuberculosis; Sensitivity and Specificity; Serologic Tests; Serology; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Tuberculosis endemic setting; Tuberculosis, Pulmonary - diagnosis; Young Adult; Serology; Tuberculosis; Tuberculosis endemic setting; Latent Mycobacterium tuberculosis infection; Ig classes; Infection; Bacteriosis; Immunoglobulins; Mycobacterial infection; Diagnosis
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2014.05.014

Summary 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.