Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

Prachi R Bapat,Ashish R Satav,Anuja P Kawle,Rajpal S Kashyap,Hatim F Daginawala,Justin J Chu,Girdhar M Taori,Hemant J Purohit,Aliabbas A Husain,Seema D Shekhawat,Pere-Joan Cardona

doi:10.1371/journal.pone.0133928

Abstract

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

Highlights

Malnourishment is the most common cause of immunodeficiency worldwide [1, 2]
body mass index (BMI)- Body mass index categorization recommended by World Health Organization (WHO)
Nutritional status of the host defines the ability of the immune system to prevent infection and disease

Summary

Introduction

Impaired immune status is an incitement for infections leading to chronic illnesses. Malnutrition and tuberculosis (TB) are both problems of considerable magnitude in most of the underdeveloped regions of the world [3]. The presence of malnutrition is a recognized risk factor for the development of TB, the association of malnutrition with the extent of disease has not been well studied. Limited efforts have been made in the identification of biomarkers for accurate diagnosis of latent TB infection (LTBI) and progression to overt disease in populations where both TB and malnutrition are widespread. The different manifestations of infection with Mycobacterium tuberculosis (M.tb) reflect the balance between the bacilli and host defense mechanisms [4]. Prevalence of malnutrition, poverty and other socio-economic problems profoundly affect the immune system accounting for greater attributable risk to TB (Fig 1) [6]

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