Session Title: Rheumatoid Arthritis: Human Etiology and Pathogenesis II
Session Type: Abstract Submissions (ACR)
Background/Purpose: Current serum measures for assessing rheumatoid arthritis (RA) are invasive and are not highly sensitive to changes in disease activity. Thus, there is a need for the discovery of additional non-invasive biomarkers for RA through an un-biased approach. Here, we postulated that urine may serve as a source of biomarkers that can reflect rheumatoid inflammation.
Methods: We found 134 novel, differentially expressed proteins (DEPs) between RA and osteoarthritis urine samples via proteomics analysis. Cellular processes enriched by DEPs were associated with cell adhesion, immune response, and proteolysis, suggesting that RA patients have inflammatory urine. After integrating the urinary DEPs with gene expression profiles in the joints and mononuclear cells, we identified 12 secretory DEPs that reflect joint pathology.
Results: Of the 12 candidates, we confirmed the increased expression of gelsolin, orosomucoid 1 and 2, and soluble CD14 (sCD14), in the RA urine via immunoassay. Moreover, urinary sCD14 had comparable diagnostic value to conventional serum biomarkers, even higher predictive power for RA activity when combined with serum C-reactive protein (CRP). Finally, we proposed a ratio of serum CRP to urinary sCD14 as a new measure for RA activity and determined a cutoff value (0.06) of the measure that minimizes false positive and negative errors.
Conclusion: This work defines the pro-inflammatory nature of rheumatoid urine, and suggests that urinary proteome profiles in RA offer new diagnostic dimensions beyond current serum parameters for disease activity.
This work was supported by grants from the Korea Healthcare technology R&D Project, the Ministry for Health, Welfare and Family Affairs (No. A092258), and the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (R31-2008-000-10103-0, R33-2008-000-10064-0, 2009-0080087, NRF-M1AXA002-2011-0028392, and R31-2008-000-10105-0).
Y. J. Park,
H. S. Kim,
S. A. Yoo,
D. H. Kim,
C. S. Cho,
W. U. Kim,
Korea Healthcare technology R&D Project,
« Back to 2013 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/discovery-of-novel-biomarkers-in-rheumatoid-urine-significance-of-urinary-cd14/