title: 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.
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Prachi R
authors.initials: PR
authors.lastname: Bapat
authors.affiliation: Meditation, AIDS, Health, Addiction & Nutrition (MAHAN) Trust, C/O Mahatma Gandhi Tribal Hospital, Karmagram, Utavali, Tahsil Dharni, District: Amravati, Maharashtra, India.
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Satav
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Aliabbas A
authors.initials: AA
authors.lastname: Husain
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Seema D
authors.initials: SD
authors.lastname: Shekhawat
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Anuja P
authors.initials: AP
authors.lastname: Kawle
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Chu
authors.affiliation: Environmental Genomic Unit, National Environmental Engineering Research Institute (NEERI), CSIR, Nehru Marg, Nagpur, India.
authors.forename: Hemant J
authors.initials: HJ
authors.lastname: Purohit
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Hatim F
authors.initials: HF
authors.lastname: Daginawala
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Girdhar M
authors.initials: GM
authors.lastname: Taori
authors.affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Rajpal S
authors.initials: RS
authors.lastname: Kashyap
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001797:Blood Protein Electrophoresis; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D018450:Disease Progression; D004198:Disease Susceptibility; D004591:Electrophoresis, Polyacrylamide Gel; D005006:Ethnicity / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D006242:Haptoglobins / Q000032:analysis*; D006801:Humans; D016867:Immunocompromised Host; D007194:India / Q000453:epidemiology; D007223:Infant; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D020738:Leptin / Q000097:blood; D008297:Male; D044342:Malnutrition / Q000453:epidemiology* / Q000276:immunology; D008875:Middle Aged; D011446:Prospective Studies; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014168:Transferrin / Q000032:analysis*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D055815:Young Adult; D000511:alpha-Macroglobulins / Q000032:analysis*
chemical_list: D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins; D020738:Leptin; D020543:Proteome; D014168:Transferrin; D000511:alpha-Macroglobulins