Journal Article

AB0740 ELEVATED SERUM SOLUBLE INTERLEUKIN-2 RECEPTOR PREDICT THE DEVELOPMENT OF UNDIFFERENTIATED ARTHRITIS

Wang, C., Su, R.

2024

Overview

Background:Abnormal autoimmunity occur before the onset of clinical rheumatoid arthritis(RA)[1]. Soluble interleukin-2 receptor (sIL-2R) is an indicator of immune activation in the body, which may be related to the activity, prognosis, and response to treatment of the disease[2, 3]. Early identification in the undifferentiated arthritis(UA) is crucial for precision therapy. In order to explore the predictive value of sIL-2R for the development of patients with UA.Objectives:We included seropositive patients (ACPA positive with or without RF positive) with undifferentiated arthritis (UA, n=27), early RA patients (Ea-RA, n=40), newly diagnosed RA patients (new RA, n=60), and patients who had been treated were readmitted due to disease activity (Relapsed RA, Re-RA, n=50). 45 healthy controls(HC) matched by sex and age were also included. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α were detected by magnetic bead multiplex immunofluorescence assay using human Th1/Th2/Th17 subsets detection kit. The level of sIL-2R was analyzed by ELISA.Methods:We included seropositive patients with undifferentiated arthritis (UA, n=27), early RA patients (Ea-RA, n=40), newly diagnosed RA patients (new RA, n=60), and patients who had been treated were readmitted due to disease activity (Relapsed RA, Re-RA, n=50). 45 healthy controls(HC) matched by sex and age were also included. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α were detected by magnetic bead multiplex immunofluorescence assay using human Th1/Th2/Th17 subsets detection kit. The level of sIL-2R was analyzed by ELISA.Results:The results showed that the serum levels of IL-2, IL-4 and IL-17 in UA, Ea-RA, New RA and Re-RA groups were significantly higher than those in HC, and the levels of IL-4 in Ea-RA and New-RA groups were increased than those in Re-RA. Moreover, the levels of IL-10, IFN-γ and TNF-α in Ea-RA, New-RA and Re-RA groups were elevated, while UA group showed no statistical difference, while the levels of IL-6 in New-RA and Re-RA groups were significantly higher than those in healthy controls. Additionally, the level of sIL-2R in the UA group was not significantly higher than that in the healthy control group, while the Ea-RA, New-RA and Re-RA groups were significantly higher than that in the HC and the UA group. In order to further assess predictive value in UA and early RA, we conducted ROC curve analysis, with an area under the curve (AUC) of 0.7952, (95% CI 0.6820 to 0.9084, p<0.0001). The cutoff value was 429 pg/ml, with a sensitivity of 70% and specificity of 73.08%. In UA, there were a total of 7 cases with sIL-2R levels greater than 429, among which 4 cases with normal ESR accounted for 57%, but had suspicious joint pain or morning stiffness symptoms, and the remaining 3 cases with elevated ESR accounted for 43%.Conclusion:Elevated levels of sIL-2R in the undifferentiated stage of arthritis may indicate the possibility of progression, which has reference value for guiding treatment.REFERENCES:[1] van Steenbergen HW, Cope AP, van der Helm-van Mil AHM.Rheumatoid arthritis prevention in arthralgia: fantasy or reality? Nat Rev Rheumatol.2023;19(12): 767-777.[2] Damoiseaux J.The IL-2 - IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin Immunol.2020;218:108515.[3] van Steenbergen HW, van Nies JA, Ruyssen-Witrand A, Huizinga TW, Cantagrel A, Berenbaum F, et al.IL2RA is associated with persistence of rheumatoid arthritis. Arthritis Res Ther.2015;17(1): 244.Figure 1.Comparison of serum cytokines in all groups.(UA(n=27), Early-RA(n=40), New-RA(n=60), ReRA(n=60),Control(n=45)).*p<0.05,**p<0.001,***p<0.0001.Figure 2.The predictive value of sIL-2R for the development of UA into early RA; A: Receiver operating curve of sIL-2R for predicting early onset of RA; B: Proportion of normal and elevated ESR in patients with sIL-2R levels greater than 429 pg/ml.Acknowledgements:NIL.Disclosure of Interests:None declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Arthralgia / Autoimmune diseases / Autoimmunity / Biomarkers / Cytokines / Cytokines and Chemokines / Enzyme-linked immunosorbent assay / Helper cells / Immune response / Immunofluorescence / Interleukin 10 / Interleukin 17 / Interleukin 2 / Interleukin 2 receptors / Interleukin 4 / Interleukin 6 / Lymphocytes T / Patients / Rheumatoid arthritis / Scientific Abstracts / Serum levels / Tumor necrosis factor-α / γ-Interferon