Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain
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Purpose: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immuneresponses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by itsstrain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immuneresponses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. Materials and Methods: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection(n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatureswere examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination isemployed. Results: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramaticallyincreased in combination with IL-6 and CXCL10 at the highest levels of specificity (95–100%). Conclusion: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information forimproved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regionswhere the M. tb Beijing/K strain is endemic.
Abstract
Purpose: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immuneresponses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by itsstrain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immuneresponses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. Materials and Methods: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection(n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatureswere examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination isemployed. Results: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramaticallyincreased in combination with IL-6 and CXCL10 at the highest levels of specificity (95–100%). Conclusion: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information forimproved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regionswhere the M. tb Beijing/K strain is endemic.
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