title: Urinary proteome profile predictive of disease activity in rheumatoid arthritis.
abstract: Current serum biomarkers for rheumatoid arthritis (RA) are not highly sensitive or specific to changes of disease activities. Thus, other complementary biomarkers have been needed to improve assessment of RA activities. In many diseases, urine has been studied as a window to provide complementary information to serum measures. Here, we conducted quantitative urinary proteome profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified 134 differentially expressed proteins (DEPs) between RA and osteoarthritis (OA) urine samples. By integrating the DEPs with gene expression profiles in joints and mononuclear cells, we initially selected 12 biomarker candidates related to joint pathology and then tested their altered expression in independent RA and OA samples using enzyme-linked immunosorbent assay. Of the initial candidates, we selected four DEPs as final candidates that were abundant in RA patients and consistent with those observed in LC-MS/MS analysis. Among them, we further focused on urinary soluble CD14 (sCD14) and examined its diagnostic value and association with disease activity. Urinary sCD14 had a diagnostic value comparable to conventional serum measures and an even higher predictive power for disease activity when combined with serum C-reactive protein. Thus, our urinary proteome provides a diagnostic window complementary to current serum parameters for the disease activity of RA.
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University , Seoul 110-799, Korea.
authors.forename: Min Jueng
authors.initials: MJ
authors.lastname: Kang
authors.forename: Yune-Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Sungyong
authors.initials: S
authors.lastname: You
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.forename: Susanna
authors.initials: S
authors.lastname: Choi
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Yi
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D015331:Cohort Studies; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000652:urine*; D008180:Lupus Erythematosus, Systemic / Q000652:urine; D010003:Osteoarthritis / Q000652:urine; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000652:urine*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D013582:Synovial Fluid / Q000502:physiology; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D002097:C-Reactive Protein
keywords: LC−MS/MS analysis; biomarkers; rheumatoid arthritis; soluble CD14; urine