Plasma Proteome Biomarkers of Inflammation in School Aged Children in Nepal

• Published in: PloS one Vol. 10; no. 12; p. e0144279
• Main Authors: Lee, Sun Eun, West, Jr, Keith P, Cole, Robert N, Schulze, Kerry J, Christian, Parul, Wu, Lee Shu-Fune, Yager, James D, Groopman, John, Ruczinski, Ingo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-12-2015; Public Library of Science (PLoS)
• Subjects: Acute phase proteins; Acute phase substances; Amyloid; Arthritis; Bioindicators; Biological markers; Biomarkers; Biomarkers - blood; Blood proteins; Blood Proteins - metabolism; C-reactive protein; Calcium; Cell adhesion & migration; Cell cycle; Child; Children; Chronic illnesses; Collagen; Development and progression; Disease; Dynamic tests; Environmental health; Extracellular matrix; Female; Gene expression; Genetic aspects; Glycoproteins; Growth factors; Health sciences; Hormones; Humans; Inflammation; Inflammation - blood; Intracellular signalling; Lipids; Male; Mass spectrometry; Mass spectroscopy; Metabolism; Micronutrients; Nepal; Nutrition; Physiological aspects; Plasma levels; Plasma proteins; Population; Population studies; Protease inhibitors; Proteinase inhibitors; Proteins; Proteome - metabolism; Proteomics; Public health; Repair; Rodents; Sex hormones; Vitamin A; Nepal; United States; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144279

Inflammation is a condition stemming from complex host defense and tissue repair mechanisms, often simply characterized by plasma levels of a single acute reactant. We attempted to identify candidate biomarkers of systemic inflammation within the plasma proteome. We applied quantitative proteomics using isobaric mass tags (iTRAQ) tandem mass spectrometry to quantify proteins in plasma of 500 Nepalese children 6-8 years of age. We evaluated those that co-vary with inflammation, indexed by α-1-acid glycoprotein (AGP), a conventional biomarker of inflammation in population studies. Among 982 proteins quantified in >10% of samples, 99 were strongly associated with AGP at a family-wise error rate of 0.1%. Magnitude and significance of association varied more among proteins positively (n = 41) than negatively associated (n = 58) with AGP. The former included known positive acute phase proteins including C-reactive protein, serum amyloid A, complement components, protease inhibitors, transport proteins with anti-oxidative activity, and numerous unexpected intracellular signaling molecules. Negatively associated proteins exhibited distinct differences in abundance between secretory hepatic proteins involved in transporting or binding lipids, micronutrients (vitamin A and calcium), growth factors and sex hormones, and proteins of largely extra-hepatic origin involved in the formation and metabolic regulation of extracellular matrix. With the same analytical approach and the significance threshold, seventy-two out of the 99 proteins were commonly associated with CRP, an established biomarker of inflammation, suggesting the validity of the identified proteins. Our findings have revealed a vast plasma proteome within a free-living population of children that comprise functional biomarkers of homeostatic and induced host defense, nutrient metabolism and tissue repair, representing a set of plasma proteins that may be used to assess dynamics and extent of inflammation for future clinical and public health application.