title: Elucidating novel serum biomarkers associated with pulmonary tuberculosis treatment.
abstract: 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.
authors: SomaLogic, Inc., Boulder, Colorado, USA.
authors: Mary A
authors: MA
authors: De Groote
authors: Payam
authors: P
authors: Nahid
authors: Leah
authors: L
authors: Jarlsberg
authors: John L
authors: JL
authors: Johnson
authors: Marc
authors: M
authors: Weiner
authors: Grace
authors: G
authors: Muzanyi
authors: Nebojsa
authors: N
authors: Janjic
authors: David G
authors: DG
authors: Sterling
authors: Urs A
authors: UA
authors: Ochsner
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054467:Phospholipases A2 / Q000097:blood; D040901:Proteomics; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000628:therapy*
chemical_list: D015415:Biomarkers; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D054467:Phospholipases A2
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