Analysis Of Serum Interleukin-2 Level And Its Correlation With Peripheral Blood Lymphocytes Subsets In Patients With Rheumatoid Arthritis

Background:Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease characterized by multiple arthritis and joint destruction.The cytokine-mediated pathway is central to the pathogenesis of RA.At the affected joint,T cells and other infiltrating immune cells associated with the disease release a variety of cytokines,which are important mediators of cell differentiation,inflammation,immune pathology,and immune response.Among them,interleukin 2(IL-2)plays an important role in this process: because it not only promotes the expansion of T cells to enhance immune response,but also promote Treg cell proliferation,control inflammation,and maintain immune tolerance.However,in RA patients,the relationships among serum IL-2 levels and disease activity,Th17/Treg immune balance,peripheral blood lymphocyte subpopulation counts,RA-specific autoantibodies and serum levels of other cytokines have rarely been reported.Therefore,the purpose of this study was to investigate the relationship between serum IL-2 levels and various clinical indicators,lymphocytes,and other cytokines in RA patients to clarify the relationship between serum IL-2 levels and RA.Objective:(1)To explore the characteristics of lymphocyte subsets in peripheral blood of RA patients with different disease activity groups;(2)To investigate the relationship between serum interleukin-2(IL-2)levels and disease activity,absolute numbers of peripheral lymphocyte subsets,autoantibodies,and associated cytokines in patients with RA.Methods:This study included 106 patients with RA,who attended the Second Hospital of Shanxi Medical University from March 2018 to October 2018,evaluated their disease activity(DAS28 score)and divided them into disease-remission(DAS28 ≤ 2.6,n = 33),low-disease-activity(2.6 < DAS28 ≤ 3.2,n = 38),and moderate-high-disease-activity(DAS28 > 3.2,n = 35)groups.Flow cytometry was used to detect the absolute numbers of peripheral lymphocyte subpopulations(T、B、NK、CD4+T、CD8+T)and CD4+ T cell subsets(Th1、Th2、Th17、Treg)in each group,and serum cytokine levels(IL-2、IL-4、IL-6、IL-10、INF-γ、TNF-α)were measured using cytometric bead array.Results:(1)Serum IL-2 levels in RA patients were positively correlated with disease activity and rheumatoid factor titers: DAS28(r = 0.339,P < 0.001)、RF(r = 0.258,P = 0.045),and multiple regression analysis revealed that serum IL-2 levels were an independent factor affecting disease activity(β = 0.237,P = 0.042);(2)Serum IL-2 levels were positively correlated with Th17/Treg ratios(r = 0.239,P= 0.013);(3)Compared with the remission group,peripheral lymphocyte and CD4+T lymphocyte subsets in patients with active RA decreased to varying degrees;however,the numbers of peripheral natural killer(NK)cells were significantly higher in the moderate-high-disease-activity group than in the remission(P = 0.046)and low-disease-activity(P= 0.020)groups;the percentages of NK cells had the same trend.In addition,the number(r = 0.230,P = 0.018)and percentage of NK(r = 0.268,P =0.006)cells were positively correlated with serum IL-2 levels.Conclusion:In RA patients,serum IL-2 levels were not only correlated with patients’ disease activity and autoantibody levels but were also involved in their Th17/Treg immune imbalance.In addition,in patients with active RA,NK cell levels were abnormally elevated,possibly due to high serum levels of IL-2.