THU0009 ASSOCIATIONS BETWEEN CYTOKINE LEVELS AND TH17/TREG IMMUNE BALANCE IN PATIENTS WITH BEHCET’S DISEASE
Authors: Yue Liu, Yan Yang, Rui Su, Xinyu Zheng, LI Xiaofeng, Caihong Wang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Behcet's disease(BD) is a chronic systemic vascular inflammatory disease.Autoimmune imbalance associated with genetic and infectious factors promotes the immune response of neutrophils and T cells, which is BD's important pathogenesis. Several studies indicate the Th17/Treg immune imbalance may play an important role in BD pathogenesis<sup>[1-2]</sup>.Although the proportion of Th17 cells was notably increased, which was accompanied by an increased levels of IL-17, IL-23<sup>[1]</sup>, whether other cytokines are associated with Th17/Treg immune balance is unclear. <h3>Objectives</h3> The aim of this study was to examine associations between levels of a broad selection of cytokines and Th17/Treg immune balance in patients with BD. <h3>Methods</h3> The study included 66 BD patients and 66 healthy controls. The absolute counts of lymphocyte subsets and CD4+T cell subsets were detected by flow cytometry for all participants.Serum levels of the following 6 cytokines were determined in the same samples using a cytometric beads array:Interleukin-2(IL-2),Interleukin-4(IL-4), Interleukin-6(IL-6),Interleukin-10(IL-10),Interferon-γ(INF-γ)and Tumor necrosis factor-α(TNF-α) for all BD patients.T tests was used to compare continuous measures.Correlations between levels of cytokines and Th17/Treg were assessed by Spearman's rank correlation tests. <h3>Results</h3> (1)Compared to healthy controls, the absolute counts of T cells were increased(<i>P</i>=0.048),the absolute counts of CD8<sup>+</sup>T cells were also increased (<i>P</i>=0.031) in BD group, the absolute counts of Th1 and Th17 cells were significantly increased(<i>P</i>&lt; 0.05)in BD group,the absolute counts of Th2 cells were decreased (<i>P</i>&lt; 0.05)in BD group,the ratio of Th1/Th2 was increased (<i>P</i>&lt; 0.001), and the ratio of Th17/Treg were increased (<i>P</i>&lt; 0.001) in BD group.There were no differences between the absolute counts of the two groups of B, NK, T+B+NK, CD4+T and Treg cells. (2)Among the investigated cytokines,the differences between the levels of IL-2,IL-6,INF-γ and normal range have statistical significance(<i>P</i>&lt; 0.001).Finally,two cytokines were positively correlated with Th17/Treg:i.e.,IL-2(<i>r</i>=0.279,<i>P</i>=0.023) and IL-4(<i>r</i>=0.260,<i>P</i>=0.035)(<i>P</i>≥ 0.2 for all other cytokines). <h3>Conclusion</h3> Our research shows that T cell homeostasis perturbation, especially Th1 and Th17 expansion and Th17/Treg immune imbalance,is the cornerstone of BD pathogenesis.These findings suggest that immune responses associated with increased levels of IL-2 and IL-4 may promote Th17/Treg immune imbalance. This also highlights the role of IL-2 and IL-4 in maintaining a balance in the Th17/Treg ratio. Further studies are required to evaluate these preliminary findings in different patient populations and also examine the possible molecular mechanisms behind our observations. <h3>References</h3> [1] Ahmadi M, Yousefi M, Abbaspour-Aghdam S, et al. Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet's disease[J]. Journal of Cellular Physiology, 2018.234(4)3985-3994.DOI:10.1002/jcp.27207. [2] Greco A, De Virgilio A, Ralli M, et al. Behcet's disease: New insights into pathophysiology, clinical features and treatment options[J]. Autoimmun Rev, 2018,17(6):567-575. DOI: 10.1016/j.autrev.2017.12.006. <h3>Disclosure of Interests</h3> None declared