血清14-3-3η蛋白水平在类风湿关节炎及脊柱关节病中的临床意义

发布时间：2018-03-25 11:11

  本文选题：类风湿关节炎　切入点：脊柱关节病　出处：《安徽医科大学》2017年硕士论文

【摘要】：研究背景类风湿关节炎(Rheumatoid arthritis,RA)是一种慢性持续性多发性以小关节为主的自身免疫性疾病。脊柱关节病(Spondyloarthropathy,Sp A)是以强直性脊柱炎(Ankylosing Spondylitis,AS)为原型,同时可累及外周关节的炎性疾病。目前RA与Sp A为临床上两种较常见的炎性关节病,早期若不及时识别及给与干预,后期均有较高的致残率,严重影响患者生活质量。因此准确的在疾病早期予以正确诊断显得尤为重要,随着疾病诊断标准的不断更新,近几年影像学如磁共振成像(MRI)亦或是超声等辅助手段在RA及Sp A的诊断中已成为热点,但其实验室诊断指标仍维持原有现状,未见有新的进展,易造成部分实验室指标阴性患者的漏诊,故寻求新的实验室指标是临床医生目前所迫切需要的。14-3-3蛋白是高度保守、几乎在所有真核生物细胞中都表达的蛋白质家族。主要包括7种亚型,可以与多种胞内蛋白质发挥相互作用,参与调节生物学过程。14-3-3η蛋白为众多亚型中的一种,目前已有研究显示,14-3-3η蛋白亚型具有配体活性,可优先激活先天免疫系统的细胞。其通过信号级联形式如细胞外信号调节激酶和p38通路上调促炎细胞因子。少量研究表明14-3-3η蛋白参与RA的发病机制,与RA的诊断、疾病活动性及疾病预后一定相关性。并且其14-3-3蛋白自身抗体与Sp A的疾病活动性以及影像学进展也有一定联系。现经文献检索关于14-3-3η蛋白与RA的研究较少,且未见有14-3-3η蛋白水平与Sp A的相关报道。本研究旨在通过测定RA及Sp A患者血清14-3-3η蛋白水平,进一步明确14-3-3η蛋白水平对于RA及Sp A诊断以及疾病的预后作用,为RA及Sp A患者的诊断及治疗提供理论依据。目的探讨血清14-3-3η蛋白水平在RA及Sp A患者中的临床意义方法选择2014年3月-2016年5月安徽医科大学第一附属医院风湿科250例住院的RA患者和222例Sp A患者,同时于体检中心同期选择80例年龄、性别想匹配的正常人(对照组)。RA患者符合ACR 1987年及2009年ACR关于RA的分类标准,Sp A患者符合2010年ASAS分类标准。采用酶联免疫吸附试验(Enzyme Linked Immunosorbent Assay,ELISA)测定RA患者、Sp A及对照组血清14-3-3η浓度。详细记录RA及Sp A患者各临床及实验室指标,采用双能X线骨密度仪测定RA患者(232例)股骨(股骨颈(neck)、Ward区、大转子、总股骨区)和腰椎(lumbar spine,L2、L3、L4、L2-4)部位BMD,160例Sp A患者行MRI检查并进行SPARCC评分。结果1.250例RA患者中有245例14-3-3η血清蛋白水平高于正常,阳性率高达98%(245/250),Sp A患者中血清14-3-3η蛋白阳性率62%(138/222),正常对照组阳性率最低5%(4/80)。三组间阳性率比较差异有统计学意义(x2=261.319,P0.0001)。RA组[2.53/(1.22-5.81)]及Sp A组[0.95/(0.54-2.09)]血清14-3-3η蛋白水平明显高于正常对照组[0.20/(0.14-0.29)],且RA组亦高于Sp A组。三组间血清14-3-3η蛋白水平比较差异有统计学意义(x2=248.694,P0.0001).并经调整检验水准(P=0.05/3)后三组间两两比较差异均有统计学意义。2.血清14-3-3η蛋白水平在对照组[0.20/(0.14-0.29)]、早期RA[3.75/(1.73-7.74)]及非早期RA[2.14/(1.19-4.23)]三组间比较有差异统计学意义(x2=176.799,P0.0001),并经调整检验水准后三组间两两比较差异均有统计学意义。且早期RA中14-3-3η蛋白水平高于非早期RA。三组间阳性率比较差异亦有统计学意义(x2=283.227,P0.0001),但早期RA 96.2%(76/79)与非早期RA 98.8%(169/171)两组间阳性率比较差异无统计学意义(P0.05)。3.在RA患者中,血清14-3-3η蛋白水平在类风湿因子(rheumatoid factor,RF)阳性与阴性分组间、抗环瓜氨酸肽(anti-cyclic citrullinated peptidesantibody,抗CCP抗体)阳性与阴性组间、DAS28分组间、有无脊柱骨折组间、有无骨质疏松(osteoporosis,OP)组间以及股骨颈区(neck)、ward区、大转子、L2、L3、L4有无OP组间差异均无统计学意义(P0.05),但OP组血清14-3-3η蛋白水平均高于无OP组。在neck、大转子、L2、L3、L4正常组、骨量减少、OP三组间差异也均无统计学意义(P0.05)。在ward区正常组[2.14/(1.19-03.96)]、骨量减少[2.21/(1.13-5.36)]及OP[3.39/(1.64-8.05)]三组间差异有统计学意义(x2=9.816,P=0.007),且14-3-3η蛋白水平梯度逐渐上升,OP组水平最高。4.在RA患者14-3-3η蛋白阳性亚组中,线性相关分析显示:血清14-3-3η蛋白水平与VAS评分(rs=0.140,P=0.029)、HAQ评分(rs=0.136,P=0.034)呈正相关,与病程(rs=-0.149,P=0.019)、Sharp评分(rs=-0.137,P=0.047)、股骨区(neck、ward区、大转子、总股骨区)及腰椎各BMD值(L2、L3、L4、L2-4)之间呈负相关(P0.05)。5.在Sp A患者中,血清14-3-3η蛋白水平在BASDAI活动与缓解组间,ASDAScrp活动与缓解组间,SPARCC评分分组间、中轴及外周脊柱关节病组间和反射学阴性及阳性组间差异均无统计学意义(P0.05)。6.在Sp A患者中,枕墙距、胸廓扩张度、腰椎活动度、指地距、VAS评分、PGA、BASFI功能评分、BASDAI1、BASDAI2、BASDAI3、BASDAI4、BASDAI5、BASDAI6、BASDAI总、ASDAScrp、SPARCC评分、ESR、CRP在血清14-3-3η蛋白阳性与阴性分组间差异均无统计学意义(P0.05)。7.在Sp A患者14-3-3η蛋白阳性亚组中,线性相关分析显示:14-3-3η蛋白与病程(rs=0.390,P0.001)、枕墙距(rs=0.300,P=0.001)、胸廓扩张度(rs=-0.204,P=0.021)、腰椎活动度(rs=-0.176,P=0.046)、SPARCC评分(rs=-0.354,P0.001)、SPARCC1(rs=-0.340,P=0.001)、SPARCC2(rs=-0.235,P=0.019)、SPARCC3(rs=-0.298,P=0.003)均呈正直线相关。8.222例Sp A患者中有48例进行了治疗前后的对比,14-3-3η蛋白治疗后相比治疗前血清水平明显降低[0.80/(0.55-1.51)]VS[1.06/(0.54-2.60)],非参数配对比较两组间差异有统计学意义(z=-2.413,P=0.016)。9.以血清14-3-3η蛋白为检验变量,RA组(1=RA组,0=正常对照组)或Sp A组(1=Sp A组,0=正常对照组)分别为效应变量。RA组ROC曲线显示:血清14-3-3η蛋白截点值为0.892ng/ml时,灵敏度为96.8%,特异度为97.5%(AUC=0.987,P0.001)。Sp A组ROC曲线显示:血清14-3-3η蛋白截点值为0.447ng/ml时,灵敏度为86.9%,特异度为92.5%(AUC=0.935,P0.001)。结论1.14-3-3η蛋白在RA组及Sp A组的血清水平明显高于对照组,且其在RA及Sp A组阳性率明显高于对照组,14-3-3η蛋白可作为正常人与炎性关节病的鉴别指标。2.14-3-3η蛋白与RA的临床症状、疾病活动性及骨质疏松的发生密切相关。3.14-3-3η蛋白水平变化可作用Sp A疗效评价之一。
[Abstract]:The research background of rheumatoid arthritis (Rheumatoid arthritis RA) is a chronic persistent multiple small joint autoimmune disease mainly. Spondylarthritis (Spondyloarthropathy Sp A) with ankylosing spondylitis (Ankylosing Spondylitis AS) as the prototype, and inflammatory disease involving the peripheral joints. At present, RA and Sp A for the two common inflammatory joint diseases, if not timely identification and early intervention, the disability rate was higher in the late, seriously affects the life quality of the patients. Therefore the accurate correct diagnosis in the early stage of the disease is particularly important, with the diagnostic standard of constantly updated, in recent years imaging such as magnetic resonance imaging (MRI) or ultrasound assisted method has become a hot spot in the diagnosis of RA and Sp in A, but the laboratory diagnostic indicators still maintain the original status, there is no new progress, causing part of the experiment Misdiagnosis of patients with negative index, the new index is clinicians seeking the lab is currently an urgent need of.14-3-3 protein is highly conserved and expressed in almost all eukaryotic cells. The protein family includes 7 subtypes, and can play a variety of intracellular protein interactions, is involved in the regulation of biological process.14-3-3 N protein is a large number of subtypes in the present study showed that 14-3-3 protein isoforms with ligand activity, can preferentially activate cells of the innate immune system. Through the signal cascade form such as extracellular signal regulated kinase p38 pathway and upregulation of proinflammatory cytokines. A few studies showed that proteins involved in the pathogenesis of 14-3-3. RA and RA, diagnosis, prognosis of disease and disease activity. And its correlated autoantibodies of 14-3-3 protein and Sp A disease activity and radiographic progression is associated The literature retrieval system. Research on 14-3-3 protein and RA in the less relevant reports and no 14-3-3 protein level and Sp A. This study aims to determine the RA and Sp in serum of patients with A 14-3-3. The protein level, 14-3-3 protein levels for ETA to further clarify the prognostic role of RA and Sp and A in the diagnosis of the disease. RA and Sp provide a theoretical basis for the diagnosis and treatment of patients with A. Objective to investigate the clinical significance of serum 14-3-3 protein levels in RA and Sp patients in A March 2014 -2016 in the Department of rheumatism of First Affiliated Hospital of Medical University Of Anhui in May 250 cases of hospitalized RA patients and 222 cases of Sp patients with A, and compared with 80 cases from physical examination center age, sex matched normal people (control group) of.RA patients with RA classification criteria of ACR 1987 and ACR 2009, Sp A who meet the 2010 ASAS classification criteria. Using enzyme-linked immunosorbent assay (Enzyme Li nked Immunosorbent Assay,ELISA)娴嬪畾RA鎮ｈ，

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