title: Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis.
abstract: To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates-gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)-in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, St Vincent's Hospital, College of Medicine, Catholic University of Korea, Suwon, Korea.|POSTECH-CATHOLIC Biomedical Engineering Institute, Catholic University of Korea, Seoul, Korea.
authors.forename: Yune-Jung
authors.initials: YJ
authors.lastname: Park
authors.affiliation: POSTECH-CATHOLIC Biomedical Engineering Institute, Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.affiliation: Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: POSTECH-CATHOLIC Biomedical Engineering Institute, Catholic University of Korea, Seoul, Korea.|Division of Rheumatology, Department of Internal Medicine, Yeouido St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.affiliation: POSTECH-CATHOLIC Biomedical Engineering Institute, Catholic University of Korea, Seoul, Korea.|Division of Rheumatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000652:urine*; D015415:Biomarkers; D002097:C-Reactive Protein; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009961:Orosomucoid / Q000652:urine; D011379:Prognosis; D020543:Proteome; D040901:Proteomics; D012372:ROC Curve; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C573095:ORM2 protein, human; D009961:Orosomucoid; D020543:Proteome; D002097:C-Reactive Protein