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

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.

Acute-phase proteins during inflammatory reaction by bacterial infection: Fish-model

“…Bapat et al . 7 observed a significant increase in α2M and haptoglobin expression in cases of Mycobacterium tuberculosis infection in humans. Enrichment of α2M with microparticles satisfactorily modulated the immune response and survival in human sepsis 33 .…”

“…To elucidate and understand the dynamics of the pathophysiological events during inflammatory reactions, variations of APPs serum levels have been studied in many diseases, such as type 2 diabetes 3 , Alzheimer’s disease 4 , the risk of Parkinson’s disease 5 , the evolution of cancers 6 and in cases of bacterial infections 7 .…”

Screening of potential biomarkers for distinguishing between latent and active tuberculosis in children using bioinformatics analysis

“…Research has shown that haptoglobin expression increased by nearly twice in patients with latent status to active TB in the malnourished population. [ 46 ] LCN2 plays an antibacterial role by combining with iron carriers required for bacterial growth. Other studies have shown that mycobactin-mediated iron uptake is a prerequisite for intracellular mycobacterial growth.…”

Alpha-2-Macroglobulin as a New Promising Biomarker Improving the Diagnostic Sensitivity of Bovine Paratuberculosis

“…Elevated plasma A2M levels in tuberculous lymphadenitis, pulmonary tuberculosis, and latent tuberculosis patients compared to healthy controls suggested a positive correlation between higher A2M levels and progression of mycobacterial infection ( 41 ). Similarly, A2M was also significantly increased in the serum of malnourished patients with active tuberculosis, suggesting a role for A2M in mycobacterial pathogenesis ( 42 ). A2M is mainly synthesized in liver and its production is affected by various cytokines such as TNF-α, IL-1 and IL-6 ( 42 ).…”

“…Similarly, A2M was also significantly increased in the serum of malnourished patients with active tuberculosis, suggesting a role for A2M in mycobacterial pathogenesis ( 42 ). A2M is mainly synthesized in liver and its production is affected by various cytokines such as TNF-α, IL-1 and IL-6 ( 42 ). In that regard, up-regulation of A2M can be induced by highly abundant pro-inflammatory cytokines in MAP-infected animal.…”