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Background: Seronegative rheumatoid arthritis (RA) is defined as RA without circulating autoantibodies, such as rheumatoid factor and anti-citrullinated protein antibodies. Thus, early diagnosis of seronegative RA can be challenging.
Objectives: We aimed to discover diagnostic biomarkers for seronegative RA versus hand osteoarthritis (OA) by lipidomics in the sera and urine of patients with RA.
Methods: We performed untargeted lipidomic analysis in sera and urine from 111 RA patients, 45 hand OA patients, and 25 healthy controls (HC). These samples were divided into a discovery cohort (n = 89) and a validation cohort (n = 92). Serum samples from patients with systemic lupus erythematosus (SLE) were additionally used for validation. The disease activity of RA patients was determined based on disease activity score in 28 joints (DAS28).
Results: The serum lipidome profile of RA was distinguishable from that of hand OA and HC. We identified a panel of ten serum lipids from the discovery cohort showing the most significant difference as potential lipid biomarker candidates for RA diagnosis. The lipid panel was tested on a validation set and achieved an accuracy of 76% with a sensitivity of 74% and a specificity of 77%. Both seropositive and seronegative patients were identified from hand OA, HC, and SLE using this panel. There were three differently expressed lipids in urine, which identified RA from HC with an accuracy of 82%. However, three urine lipids did not differentiate RA from hand OA. Between seronegative and seropositive RA, 8 lipid pathways were different.
Conclusion: A panel of 10 serum lipids were selected from lipidomics that could aid in diagnosing seronegative RA patients, differentiating not only from HC but also from patients with hand OA.
REFERENCES: [1] H. Luan, W. Gu, H. Li, Z. Wang, L. Lu, M. Ke, J. Lu, W. Chen, Z. Lan, Y. Xiao, J. Xu, Y. Zhang, Z. Cai, S. Liu, W. Zhang, Serum metabolomic and lipidomic profiling identifies diagnostic biomarkers for seropositive and seronegative rheumatoid arthritis patients, J. Transl. Med. 19 (2021) 1–10.
[2] J.H. Koh, S.J. Yoon, M. Kim, S. Cho, J. Lim, Y. Park, H.S. Kim, S.W. Kwon, W.U. Kim, Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis, Exp. Mol. Med. 54 (2022) 143–155.
Acknowledgements: This work was supported by grants from the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2015R1A3A2032927 to WU Kim).
Disclosure of Interests: None declared.