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

Chin-Chung Shu,Ming-Fang Wu,Chia-Lin Hsu,Chong-Jen Yu,Shie-Liang Hsieh,Chun-Ta Huang,Li-Na Lee,Pan-Chyr Yang,Jann-Yuan Wang

doi:10.1186/1471-2334-13-45

Abstract

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

Highlights

Apoptosis-associated biomarkers are rarely studied, especially their role in predicting the development of tuberculosis (TB) from latent TB infection and in prognostication
Between the non-infection and latent TB infection (LTBI) groups, there was no significant difference in serum levels of biomarkers except for monocyte chemotactic protein (MCP)-1 (27.86 vs. 18.30 pg/ml, p=0.039)
Using four groups of data that represent the different stages in the development of active TB disease, the present study reveals that apoptosis-associated biomarkers change significantly

Summary

Introduction

Apoptosis-associated biomarkers are rarely studied, especially their role in predicting the development of tuberculosis (TB) from latent TB infection and in prognostication. Tuberculosis (TB) remains one of the most important infectious diseases worldwide. According to estimates of the World Health Organization (WHO), 3 hundred million people were infected by Mycobacterium tuberculosis and 30 million people died of TB from 2001 to 2010 [1,2]. In Taiwan, the incidence of TB remains high (58 per 100,000 population in 2009) [3]. Early diagnosis and timely treatment are the most important strategies [4,5]. Patients infected with M. tuberculosis will develop latent TB infection (LTBI), a major source of active TB [6]. Previous studies show that about 10% of LTBI

Methods

Results

Discussion

Conclusion