Elucidating novel serum biomarkers associated with pulmonary tuberculosis treatment

• Published in: PloS one 2013-04, Vol.8 (4), p.e61002-e61002
• Main Authors: De Groote, Mary A, Nahid, Payam, Jarlsberg, Leah, Johnson, John L, Weiner, Marc, Muzanyi, Grace, Janjic, Nebojsa, Sterling, David G, Ochsner, Urs A
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Antithrombin; Apoptosis; Aptamers; Biological activity; Biological response modifiers; Biology; Biomarkers; Biomarkers - blood; C-Reactive Protein - metabolism; Cavitation; Cell cycle; Clinical trials; Coagulation; Consortia; Critical care; Deoxyribonucleic acid; Disease control; DNA; Drug therapy; Female; Gene expression; Healing; Humans; Immunity; Immunology; Infectious diseases; Interferon; Lung cancer; Male; Mathematics; Medical research; Medical treatment; Medicine; Metabolism; Middle Aged; Multiplexing; Pathways; Pattern recognition; Phospholipase A2; Phospholipases A2 - blood; Proteases; Proteins; Proteomics; Respiratory system agents; Serum Amyloid A Protein - metabolism; Therapy; Tissue inhibitor of metalloproteinase 2; Tuberculosis; Tuberculosis, Pulmonary - therapy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0061002

In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO) to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Prevention's Tuberculosis Trials Consortium (TBTC) Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB). We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy.