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Open Access Highly Accessed Research article

Apoptosis-associated biomarkers in tuberculosis: promising for diagnosis and prognosis prediction

Chin-Chung Shu12, Ming-Fang Wu45, Chia-Lin Hsu3, Chun-Ta Huang12, Jann-Yuan Wang3*, Shie-Liang Hsieh45, Chong-Jen Yu3, Li-Na Lee36 and Pan-Chyr Yang3

Author Affiliations

1 Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan

2 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

3 Department of Internal Medicine, National Taiwan University Hospital, # 7, Chung-Shan South Road, Taipei 100, Taiwan

4 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan

5 Institute of Clinical Medicine & Infection and Immunity Center, National Yang-Ming University, Taipei, Taiwan

6 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

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BMC Infectious Diseases 2013, 13:45  doi:10.1186/1471-2334-13-45

Published: 28 January 2013

Abstract

Background

Apoptosis-associated biomarkers are rarely studied, especially their role in predicting the development of tuberculosis (TB) from latent TB infection and in prognostication.

Methods

Patients with TB and interferon-gamma release assay (IGRA)-positive and IGRA-negative family contacts were evaluated to analyze changes in apoptosis-associated serum biomarkers, which included decoy receptor 3 (DcR3), prostaglandin 2 (PGE2), and lipoxin. The prognostic implications of these serum biomarkers were also analyzed.

Results

One hundred TB patients and 92 IGRA-negative and 91 IGRA-positive family contacts were recruited. The DcR3 and PGE2 levels decreased from the IGRA-negative group to the IGRA-positive group, and peaked in the TB group. Lipoxin decreased to trough in the TB group. The three apoptosis serum markers and age were independent factors discriminating active TB from latent TB infection. In active TB, older age, co-morbidity, and higher serum DcR3 and monocyte chemotactic protein (MCP)-1 were independently associated with poorer six-month survival.

Conclusion

Apoptosis-associated serum biomarkers change along with the status of Mycobacterium tuberculosis infection. In close contacts with positive IGRA, high DcR3 and PGE2 and low lipoxin may increase the probability of active TB. Older age, co-morbidity, and high DcR3 and MCP-1 levels might be important prognostic factors that warrant further investigation.

Keywords:
Apoptosis; Decoy receptor 3; Latent tuberculosis infection; Lipoxin; Prostaglandin E2; Tuberculosis