目的：探究程序性细胞死亡因子5（programmed cell death factor 5,PDCD5）在类风湿关节炎（rheumatoid arthritis, RA）患者中的表达情况,并探讨PDCD5在RA发病中的可能作用。方法：采用酶联免疫吸附试验检测36例活动性RA患者和35例骨关节炎（osteoarthritis,OA）患者的血清和关节液中的PDCD5、白细胞介素6（interleukin 6,IL-6）水平,另以33名健康人的血清PDCD5水平作为对照（对照组）,比较3组间以上各指标水平的差异。同时再检测RA患者的C反应蛋白（C reaction protein, CRP）、红细胞沉降率（erythrocyte sedimentation rate, ESR）、类风湿因子（rheumatoid factor,RF）和环瓜氨酸肽（cyclic citrullinated peptide, CCP）,记录其肿胀关节数（swollen joint count,SJC）、疼痛关节数（tender joints count, TJC）,作为疾病活动指数参考指标。结果：RA组的血清PDCD5水平[（32.47±12.79） ng/mL]显著高于OA组[（12.79±9.84） ng/mL]及对照组[（18.40±18.97） ng/mL];RA组关节液中的PDCD5水平[（47.75±21.94） ng/mL]亦高于OA组[（19.33±11.25） ng/mL]。RA患者血清中的PDCD5水平与IL-6水平呈负相关（r=-0.431）,但在关节液中未观察到两者间具有相关性。Pearson分析显示,RA患者血清中的PDCD5水平与CRP、ESR、SJC、TJC呈负相关（R值分别为-0.523、-0.701、-0.845、-0.943）,但与CCP及RF水平间无统计学相关性。结论：活动性RA患者的血清及关节液中PDCD5的水平升高,而其表达失调可能与IL-6水平相关。
Objective: To investigate the expression of programmed cell death factor 5 ( PDCD5) in patients with rheumatoid arthritis (RA) and to explore its potential role in the pathogenesis of RA. Methods: A total of 36 patients with RA and 35 patients with osteoarthritis (OA) were enrolled, and 33 healthy people were served as controls. PDCD5 and IL-6 levels in serum as well as the levels in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Indices including C reaction protein (CRP), erythrocyte sedimentation rate(ESR), rheumatoid factor(RF）and cyclic citrullinated protein (CCP）were also detected, while count of swollen joints (SJC) and count of tender joints (TJC) served as reference of disease activity were recorded. Results: Compared with OA patients and controls, RA patients had a higher serum level of PDCD5 [（32.47±12.79） ng/mL vs （12.79±9.84） ng/mL in OA and (18.40±18.97） ng/mL in controls]. PDCD5 levels in synovial fluid of RA patients were also higher than those of OA patients. Furthermore, serum level of PDCD5 in RA patients was negatively correlated with IL-6 level in serum, however, no correlation was observed in synovial fluid. Pearson analysis showed that serum PDCD5 level in RA was negatively correlated with CRP, ESR, TJC and SJC (R=-0.523, -0.701, -0.845, -0.943, respectively), but had no correlation with RF and CCP. Conclusions: Serum and synovial levels of PDCD5 could reflect the activity of RA, and its abnormal expression may be associated with level of IL-6.
[1] Yu C, Jin SY, Li MT, et al.Current status of rheumatoid arthritis registries and prevalence of remission[J]. Zhonghua Nei Ke Za Zhi,2018,57(3):175-178.
[2] Firestein GS.Evolving concepts of rheumatoid arthritis[J]. Nature,2003,423(6937):356-361.
[3] Wang W, Song XW, Zhao CH.Roles of programmed cell death protein 5 in inflammation and cancer(Review)[J]. Int J Oncol,2016,49(5):1801-1806.
[4] Jiang J, Wang N, Guan Z, et al.Programmed cell death 5 factor enhances triptolide-induced fibroblast-like synoviocyte apoptosis of rheumatoid arthritis[J]. Artif Cells Blood Substit Immobil Biotechnol,2010,38(1):38-42.
[5] Brzustewicz E, Bryl E.The role of cytokines in the pathogenesis of rheumatoid arthritis--Practical and potential application of cytokines as biomarkers and targets of personalized therapy[J]. Cytokine,2015,76(2):527-536.
[6] Braun J, Sieper J.Classification criteria for rheumatoid arthritis and ankylosing spondylitis[J]. Clin Exp Rheumatol,2009,27(4 Suppl 55):S68-S73.
[7] Zhang W, Doherty M, Peat G, et al.EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis[J]. Ann Rheum Dis,2010,69(3):483-489.
[8] Gu X, Gu B, Lv X, et al.1, 25-dihydroxy-vitamin D3 with tumor necrosis factor-alpha protects against rheumatoid arthritis by promoting p53 acetylation-mediated apoptosis via Sirt1 in synoviocytes[J]. Cell Death Dis,2016,7(10):e2423.
[9] Zhu A, Wang M, Zhou G, et al.Fas/FasL, Bcl2 and Caspase-8 gene polymorphisms in Chinese patients with rheumatoid arthritis[J]. Rheumatol Int,2016,36(6):807-818.
[10] Zhao M, Li Y, Xiao W.Anti-apoptotic effect of interleukin-22 on fibroblast-like synoviocytes in patients with rheumatoid arthritis is mediated via the signal transducer and activator of transcription 3 signaling pathway[J]. Int J Rheum Dis,2017,20(2):214-224.
[11] Leech M, Xue JR, Dacumos A, et al.The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response[J]. Clin Exp Immunol,2008,152(2):345-353.
[12] Jiang J, Wang N, Guan Z, et al.Programmed cell death 5 factor enhances triptolide-induced fibroblast-like synoviocyte apoptosis of rheumatoid arthritis[J]. Artif Cells Blood Substit Immobil Biotechnol,2010,38(1):38-42.
[13] Noack M, Miossec P.Selected cytokine pathways in rheumatoid arthritis[J]. Semin Immunopathol,2017,39(4):365-383.
[14] 刘娜, 徐建华. IL-6在类风湿关节炎合并系统损害中的作用机制研究进展[J]. 安徽医学,2017,38(5):658-661.
[15] 刘玮, 吴歆, 徐沪济. 类风湿关节炎易感基因遗传背景的研究进展[J]. 诊断学理论与实践,2018,17(3):347-351.
