發(fā)布時間：2018-03-25 11:11

  本文選題：類風濕關(guān)節(jié)炎　切入點：脊柱關(guān)節(jié)病　出處：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：研究背景類風濕關(guān)節(jié)炎(Rheumatoid arthritis,RA)是一種慢性持續(xù)性多發(fā)性以小關(guān)節(jié)為主的自身免疫性疾病。脊柱關(guān)節(jié)病(Spondyloarthropathy,Sp A)是以強直性脊柱炎(Ankylosing Spondylitis,AS)為原型,同時可累及外周關(guān)節(jié)的炎性疾病。目前RA與Sp A為臨床上兩種較常見的炎性關(guān)節(jié)病,早期若不及時識別及給與干預,后期均有較高的致殘率,嚴重影響患者生活質(zhì)量。因此準確的在疾病早期予以正確診斷顯得尤為重要,隨著疾病診斷標準的不斷更新,近幾年影像學如磁共振成像(MRI)亦或是超聲等輔助手段在RA及Sp A的診斷中已成為熱點,但其實驗室診斷指標仍維持原有現(xiàn)狀,未見有新的進展,易造成部分實驗室指標陰性患者的漏診,故尋求新的實驗室指標是臨床醫(yī)生目前所迫切需要的。14-3-3蛋白是高度保守、幾乎在所有真核生物細胞中都表達的蛋白質(zhì)家族。主要包括7種亞型,可以與多種胞內(nèi)蛋白質(zhì)發(fā)揮相互作用,參與調(diào)節(jié)生物學過程。14-3-3η蛋白為眾多亞型中的一種,目前已有研究顯示,14-3-3η蛋白亞型具有配體活性,可優(yōu)先激活先天免疫系統(tǒng)的細胞。其通過信號級聯(lián)形式如細胞外信號調(diào)節(jié)激酶和p38通路上調(diào)促炎細胞因子。少量研究表明14-3-3η蛋白參與RA的發(fā)病機制,與RA的診斷、疾病活動性及疾病預后一定相關(guān)性。并且其14-3-3蛋白自身抗體與Sp A的疾病活動性以及影像學進展也有一定聯(lián)系。現(xiàn)經(jīng)文獻檢索關(guān)于14-3-3η蛋白與RA的研究較少,且未見有14-3-3η蛋白水平與Sp A的相關(guān)報道。本研究旨在通過測定RA及Sp A患者血清14-3-3η蛋白水平,進一步明確14-3-3η蛋白水平對于RA及Sp A診斷以及疾病的預后作用,為RA及Sp A患者的診斷及治療提供理論依據(jù)。目的探討血清14-3-3η蛋白水平在RA及Sp A患者中的臨床意義方法選擇2014年3月-2016年5月安徽醫(yī)科大學第一附屬醫(yī)院風濕科250例住院的RA患者和222例Sp A患者,同時于體檢中心同期選擇80例年齡、性別想匹配的正常人(對照組)。RA患者符合ACR 1987年及2009年ACR關(guān)于RA的分類標準,Sp A患者符合2010年ASAS分類標準。采用酶聯(lián)免疫吸附試驗(Enzyme Linked Immunosorbent Assay,ELISA)測定RA患者、Sp A及對照組血清14-3-3η濃度。詳細記錄RA及Sp A患者各臨床及實驗室指標,采用雙能X線骨密度儀測定RA患者(232例)股骨(股骨頸(neck)、Ward區(qū)、大轉(zhuǎn)子、總股骨區(qū))和腰椎(lumbar spine,L2、L3、L4、L2-4)部位BMD,160例Sp A患者行MRI檢查并進行SPARCC評分。結(jié)果1.250例RA患者中有245例14-3-3η血清蛋白水平高于正常,陽性率高達98%(245/250),Sp A患者中血清14-3-3η蛋白陽性率62%(138/222),正常對照組陽性率最低5%(4/80)。三組間陽性率比較差異有統(tǒng)計學意義(x2=261.319,P0.0001)。RA組[2.53/(1.22-5.81)]及Sp A組[0.95/(0.54-2.09)]血清14-3-3η蛋白水平明顯高于正常對照組[0.20/(0.14-0.29)],且RA組亦高于Sp A組。三組間血清14-3-3η蛋白水平比較差異有統(tǒng)計學意義(x2=248.694,P0.0001).并經(jīng)調(diào)整檢驗水準(P=0.05/3)后三組間兩兩比較差異均有統(tǒng)計學意義。2.血清14-3-3η蛋白水平在對照組[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)]三組間比較有差異統(tǒng)計學意義(x2=176.799,P0.0001),并經(jīng)調(diào)整檢驗水準后三組間兩兩比較差異均有統(tǒng)計學意義。且早期RA中14-3-3η蛋白水平高于非早期RA。三組間陽性率比較差異亦有統(tǒng)計學意義(x2=283.227,P0.0001),但早期RA 96.2%(76/79)與非早期RA 98.8%(169/171)兩組間陽性率比較差異無統(tǒng)計學意義(P0.05)。3.在RA患者中,血清14-3-3η蛋白水平在類風濕因子(rheumatoid factor,RF)陽性與陰性分組間、抗環(huán)瓜氨酸肽(anti-cyclic citrullinated peptidesantibody,抗CCP抗體)陽性與陰性組間、DAS28分組間、有無脊柱骨折組間、有無骨質(zhì)疏松(osteoporosis,OP)組間以及股骨頸區(qū)(neck)、ward區(qū)、大轉(zhuǎn)子、L2、L3、L4有無OP組間差異均無統(tǒng)計學意義(P0.05),但OP組血清14-3-3η蛋白水平均高于無OP組。在neck、大轉(zhuǎn)子、L2、L3、L4正常組、骨量減少、OP三組間差異也均無統(tǒng)計學意義(P0.05)。在ward區(qū)正常組[2.14/(1.19-03.96)]、骨量減少[2.21/(1.13-5.36)]及OP[3.39/(1.64-8.05)]三組間差異有統(tǒng)計學意義(x2=9.816,P=0.007),且14-3-3η蛋白水平梯度逐漸上升,OP組水平最高。4.在RA患者14-3-3η蛋白陽性亞組中,線性相關(guān)分析顯示:血清14-3-3η蛋白水平與VAS評分(rs=0.140,P=0.029)、HAQ評分(rs=0.136,P=0.034)呈正相關(guān),與病程(rs=-0.149,P=0.019)、Sharp評分(rs=-0.137,P=0.047)、股骨區(qū)(neck、ward區(qū)、大轉(zhuǎn)子、總股骨區(qū))及腰椎各BMD值(L2、L3、L4、L2-4)之間呈負相關(guān)(P0.05)。5.在Sp A患者中,血清14-3-3η蛋白水平在BASDAI活動與緩解組間,ASDAScrp活動與緩解組間,SPARCC評分分組間、中軸及外周脊柱關(guān)節(jié)病組間和反射學陰性及陽性組間差異均無統(tǒng)計學意義(P0.05)。6.在Sp A患者中,枕墻距、胸廓擴張度、腰椎活動度、指地距、VAS評分、PGA、BASFI功能評分、BASDAI1、BASDAI2、BASDAI3、BASDAI4、BASDAI5、BASDAI6、BASDAI總、ASDAScrp、SPARCC評分、ESR、CRP在血清14-3-3η蛋白陽性與陰性分組間差異均無統(tǒng)計學意義(P0.05)。7.在Sp A患者14-3-3η蛋白陽性亞組中,線性相關(guān)分析顯示:14-3-3η蛋白與病程(rs=0.390,P0.001)、枕墻距(rs=0.300,P=0.001)、胸廓擴張度(rs=-0.204,P=0.021)、腰椎活動度(rs=-0.176,P=0.046)、SPARCC評分(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)均呈正直線相關(guān)。8.222例Sp A患者中有48例進行了治療前后的對比,14-3-3η蛋白治療后相比治療前血清水平明顯降低[0.80/(0.55-1.51)]VS[1.06/(0.54-2.60)],非參數(shù)配對比較兩組間差異有統(tǒng)計學意義(z=-2.413,P=0.016)。9.以血清14-3-3η蛋白為檢驗變量,RA組(1=RA組,0=正常對照組)或Sp A組(1=Sp A組,0=正常對照組)分別為效應(yīng)變量。RA組ROC曲線顯示:血清14-3-3η蛋白截點值為0.892ng/ml時,靈敏度為96.8%,特異度為97.5%(AUC=0.987,P0.001)。Sp A組ROC曲線顯示:血清14-3-3η蛋白截點值為0.447ng/ml時,靈敏度為86.9%,特異度為92.5%(AUC=0.935,P0.001)。結(jié)論1.14-3-3η蛋白在RA組及Sp A組的血清水平明顯高于對照組,且其在RA及Sp A組陽性率明顯高于對照組,14-3-3η蛋白可作為正常人與炎性關(guān)節(jié)病的鑒別指標。2.14-3-3η蛋白與RA的臨床癥狀、疾病活動性及骨質(zhì)疏松的發(fā)生密切相關(guān)。3.14-3-3η蛋白水平變化可作用Sp A療效評價之一。
[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)嫻嬪畾RA鎮(zhèn)ｈ，

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