多种自身抗体在老年类风湿关节炎诊断中的临床应用价值

目的：探讨抗环瓜氨酸（CCP）抗体、抗角蛋白（AKA）抗体、抗核周因子（APF）和RA33抗体在老年起病类风湿关节炎（EORA）诊断和鉴别诊断中的临床意义。方法：对95例EORA（EORA组）、69例风湿性多肌痛（PMR）患者（PMR组）和47例健康者（对照组）进行抗CCP抗体、AKA、APF和RA33抗体检测,其中抗CCP抗体和RA33抗体采用酶联免疫吸附法（ELISA法）检测,AKA和APF采用间接免疫荧光法（ⅡF）法检测。结果：①抗CCP抗体、AKA、APF和RA33抗体在EORA组的敏感性和特异性分别为（58．9％、95．8％）、（33．7％、91．4％）、（31．6％、89．4％）和（36．8％、86．7％）,显著高于PMR组和对照组（P〈0．01）。②EORA组抗CCP抗体的敏感性显著高于AKA、APF和RA33抗体（P〈0．05）。联合检测4种抗体,敏感性有所降低,但使阳性率提高至98．9％,且有更高的阳性预测值。③69例PMR患者中有6例患者CCP抗体阳性,3例AKA阳性,且与CCP抗体相重叠,2例APF阳性,2例RA33阳性,1年后3例重叠阳性的PMR患者确诊为EORA。结论：PMR与EORA有相似的临床症状和特征,临床上有时难以鉴别,极少数病例,在早期不典型时易误诊,但抗CCP抗体、AKA、APF和RA33抗体仍主要出现在EORA患者中,尤其抗CCP抗体有较高的敏感性和特异性,4种抗体联合检测有更高的特异性和阳性预测值,同时结合临床症状、影像学改变等,4种抗体联合检测对EORA的诊断和鉴别诊断有很高的临床应用价值。     

抗环瓜氨酸肽抗体和抗角蛋白抗体在老年发病类风湿关节炎诊断中的意义

目的 研究抗环瓜氨酸肽(CCP)抗体、抗角蛋白抗体(AKA)在老年发病类风湿关节炎(EORA)中的临床意义.方法 检测69例EORA患者和42例风湿性多肌痛(PMR)患者中的两种抗体,其中抗CCP抗体采用ELISA法,AKA采用间接免疫荧光(IIF)法检测.结果 EORA组两种抗体的阳性率显著高于PMR组(P＜0.05),两种抗体诊断EORA的敏感性和特异性分别为:抗CCP抗体(55.1%、94.3%)、AKA(33.3%、91.5%),抗CCP抗体和AKA合用敏感性有所降低,但能使特异性增高至98.3%.结论 抗CCP抗体有很高的敏感性和特异性,抗CCP抗体和AKA在EORA组中的阳性率明显高于PMR组,两种抗体联合检测使特异性提高近100%,有利于EORA的鉴别诊断,结合影像学改变,对提高EORA的诊断率也有临床应用价值.     

抗CCP抗体和抗RA33抗体对老年类风湿关节炎诊断的意义

目的 同时检测抗环瓜氨酸肽抗体（抗CCP抗体）、抗RA33抗体和类风湿因了（RF）在老年类风湿关节炎（EORA）中的敏感度及特异度，探讨三者联合检测在EORA中的意义。方法 采用ELISA检测抗CCP抗体及抗RA33抗体，用速率散射比浊法量检测类风湿因子（RF）。共检测26例EORA病人、25例非EORA、30例正常老年人中的抗CCP抗体、抗RA33抗体及RF的分布。比较三者之间的敏感度、特异度及三者联合检测的结果。结果 抗CCP抗体、抗RA33抗体及RF对RA的敏感度分别为46.15%、34.62%、61.54%，特异度分别为98.18%、96.36%、83.63%。抗CCP抗体敏感度特异度与抗RA33抗体敏感度差异无显著性（P〉0.05），抗CCP抗体和抗RA33抗体特异度与RF特异度比较差异有显著性（P〈0.05）。抗CCP抗体敏感度特异度与抗RA33抗体与RF的关系不密切。结论 抗CCP抗体和RA33抗体具有良好的敏感性及特异性，与RF联合检测能提高诊断EORA的敏感性和特异性。     

血清抗角蛋白抗体抗环瓜氨酸肽抗体和类风湿因子在类风湿关节炎中的意义

目的 评价抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)中的意义.方法 收集82例RA患者及56例非RA患者,测定其抗CCP抗体、AKA和RF水平,评价对RA诊断的敏感性、特异性,比较RA患者中抗CCP抗体、AKA阳性组和阴性组的压痛关节数、肿胀关节数、红细胞沉降率(ESR)、C反应蛋白(CRP)、疾病活动指数(DAS)、Ritchie's指数(RAI).结果 单独检测AKA、抗CCP抗体、RF及联合检测的曲线下面积都较高(P<0.05).抗CCP抗体、AKA的特异度分别为92.9%、91.1%,联合检测AKA、抗CCP抗体和RF有任何一种及以上阳性的灵敏度最高,为95.1%.抗CCP抗体阳性组与阴性组的关节肿胀数、关节压痛数、ESR、CRP、DAS、RAI差异有统计学意义(P<0.05);AKA阳性组与阴性组的关节肿胀数、ESR、DSA差异均有统计学意义(P<0.05).结论 联合检测抗CCP抗体、RF、AKA对诊断RA有意义,抗CCP抗体、AKA可能与RA的活动度相关.     

抗环瓜氨酸肽抗体、抗角蛋白抗体、抗核周因子抗体和类风湿因子联合检测在老年类风湿性关节炎诊断中的意义

目的 探讨抗环瓜氨酸肽抗体(CCP)、抗角蛋白抗体(AKA)、抗核周因子抗体(APF)和类风湿因子(RF)联合检测在老年类风湿关节炎(RA)诊断中的应用价值.方法 分别采用酶联免疫、间接免疫荧光、斑点免疫荧光和免疫散射比浊法检测83例老年RA患者血清中抗CCP抗体、AKA、AFP和RF.结果 抗CCP抗体灵敏度为50.6%,特异性96.3%;AKA检测灵敏度为38.6%,特异性96.3%;APF检测灵敏度为57.8%,特异性95.3%;RF灵敏度为77.1%,特异性83.2%;抗CCP+AKA+APF+RF四种自身抗体联合检测灵敏度19.2%,特异性100%.结论 CCP、AKA、APF及RF四种抗体联合检测,提高了老年RA的诊断率.     

抗瓜氨酸化蛋白抗体联合检测在类风湿关节炎中诊断价值的分析

目的 分别检测抗核周因子(APF)、抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体,比较3种抗体在类风湿关节炎(RA)诊断中的敏感性和特异性,并探讨3种抗体联合检测在RA中的诊断价值.方法 选取2006-2008年在北京大学人民医院风湿免疫科就诊、具有关节症状的各种风湿病患者551例,其中,RA患者304例,其他风湿病患者247例.所有患者均检测APF、AKA和抗CCP抗体,其中J前两者采用间接免疫荧光法(IIF)检测,后者采用酶联免疫吸附试验(ELISA)法检测.结果 抗CCP抗体、AKA和APF对RA诊断的敏感性分别为76.2%、43.6%和34.5%,特异性分别为96.0%、98.4%和99.6%;3种抗体中任一抗体阳性对RA诊断的敏感性和特异性分别为77.3%和94.7%;3种抗体中任2项抗体阳性对RA诊断的敏感性和特异性分别为48.4%和99.2%,而3种抗体均阳性对RA诊断的特异性达100%,但敏感性仅28.3%.结论 3种抗瓜氨酸化蛋白抗体中,以抗CCP抗体对RA的诊断价值最高,联合检测抗CCP抗体、AKA和APF并不能显著提高对RA的诊断价值.     

抗环瓜氨酸肽抗体对老年发病的类风湿关节炎诊断意义的研究

目的探讨抗环瓜氨酸肽（CCP）抗体对老年类风湿关节炎（EORA）的诊断意义。方法应用ELISA方法对EORA组（n=30）、风湿性多肌痛（PMR）组（n=27）、骨关节炎（OA）组（n=30）、健康对照组（n=30）血清抗CCP抗体水平进行检测,并研究其与EORA患者病情活动度的关系。结果抗CCP抗体对EORA诊断的敏感性、特异性、阳性预测值及阴性预测值均明显高于类风湿因子（RF）,抗CCP抗体水平与EORA患者疾病活动度呈明显正相关（r=0.419,P=0.021）。结论抗CCP抗体检测有助于EORA的诊断,是病情活动性的指标。     

抗环瓜氨酸肽抗体在类风湿关节炎中的意义

目的探讨抗环瓜氨酸肽(CCP)抗体在类风湿关节炎(RA)诊断治疗中的意义。方法采用酶联免疫吸附试验(ELISA)法分别测定40例RA患者、56例其他风湿病患者的抗CCP抗体、类风湿因子IgM-RF、IgG-RF及类风湿因子(RF),同时比较20例RA患者治疗前后抗CCP抗体的水平变化。结果(1)RA组的抗CCP抗体水平显著高于其他风湿病组(P<0.01),抗CCP抗体对RA的敏感性和特异性分别为80%、85.7%,与RF比较其特异性、阳性预测值之间差异有显著性(P均<0.05)。(2)抗CCP抗体与IgM-RF、IgG-RF联合检测中,二项联合检测的特异性为96.4%,三项联合检测的特异性为98.2%,与单独检测抗CCP抗体、RF有更高的特异性。(3)20例RA患者治疗后抗CCP抗体水平显著下降(P<0.05)。结论抗CCP抗体对RA诊断具有良好的敏感性和特异性,可用于RA的临床诊断。抗CCP抗体与IgM-RF、IgG-RF联合检测可提高RA的早期诊断率。抗CCP抗体还可作为临床活动指标之一。     

抗环瓜氨酸肽抗体在风湿性多肌痛与老年发病类风湿关节炎鉴别诊断中的意义

风湿性多肌痛（polymyalgia rheumatica,PMR）是病因不明的炎症性疾病.部分老年发病类风湿关节炎（elderly-onset rheumatoid arthritis,EORA）患者存在PMR样临床表现,有时与PMR不容易鉴别.近年来的研究发现,抗环瓜氨酸肽（cyclic citrullinated peptide,CCP）抗体诊断类风湿关节炎（RA）有较高的敏感性和特异性.本研究随访一组PMR患者血清抗CCP抗体,并结合影像学检查,了解该抗体在PMR与EORA鉴别诊断中的意义.     

RF、AKA、APF、抗CCP抗体联合检测对老年类风湿关节炎的诊断价值

目的研究类风湿因子(RF)、抗环瓜氨酸(CCP)抗体、抗角蛋白抗体(AKA)、抗核周因子抗体(APF)对老年类风湿关节炎(RA)的诊断价值。方法 RA患者480例为RA组,非RA自身免疫病患者300例为非RA组,健康组300例,对受检者进行RF、抗CCP抗体、AKA、APF检测。结果 RA组分别与非RA组和健康组比较,4种检测标志物阳性检出率均有显著性差异(P0.05)。单项指标比较,RF有较高的灵敏度,但特异性明显低于其他3个指标(P0.05),AKA、APF虽有较高的特异度,但灵敏度低(P0.05),抗CCP抗体有较高的灵敏度和特异度。对RA组各指标联合检测,以上指标任意2个组合比3项(抗CCP抗体+RF+APF,抗CCP抗体+RF+AKA)、4项(抗CCP抗体+RF+APF+AKA)联合检测敏感度低(P0.05),而特异度均较高,但没有明显差异(P0.05)。4项联合检测灵敏度及特异度达到最高。结论单项指标比较,抗CCP抗体有较高的灵敏度和特异度。联合指标比较,以抗CCP抗体+RF+APF或抗CCP抗体+RF+AKA3项联合检测模式诊断RA具有较高的价值,便于临床医师早期确诊,减少漏诊误诊病例。     

Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis

BACKGROUND: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria. OBJECTIVE: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis. METHODS: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone. RESULTS: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF >or=50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF >or=50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease. CONCLUSIONS: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.     

抗CCP、抗RA33和RF在类风湿关节炎诊断中的作用

目的探讨抗环瓜氨酸肽抗体（anti-ccp）、抗RA33抗体和类风湿因子对类风湿关节炎（RA）的诊断意义.方法对RA（104例）和其他风湿性疾病患者（75例）,以及健康成人（40例）的血清进行检测,应用ELISA法检测抗CCP抗体和抗RA33抗体,乳胶凝集法检测RF.结果抗CCP对RA诊断敏感性56.7%,特异性100%;抗RA33对RA诊断的敏感性28.8%,特异性90.7%;RF对RA诊断的敏感性72%,特异性62.7%;RF与抗CCP和抗RA33同时检测敏感性提高到84.6%,特异性提高到100%.37.9%和17.2%RF阴性的RA患者分别有抗CCP和抗RA33阳性.结论抗CCP和抗RA33对RA诊断特异性优于RF（P＜0.05）,三者同时检测是RA较理想的血清学诊断方法.     

Clinical utility of anti-CCP antibodies in the differential diagnosis of elderly-onset rheumatoid arthritis and polymyalgia rheumatica

BACKGROUND: In a significant number of patients the differential diagnosis between elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) is very difficult because of the lack of specific serum markers. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) have recently been shown to be highly specific for rheumatoid arthritis (RA). This is the first study addressing the utility of these antibodies in the differential diagnosis between EORA and PMR. METHODS: Serum samples from 57 EORA patients and 49 PMR patients were studied for the presence of anti-CCP Abs and rheumatoid factor (RF). As controls, samples from 41 RA patients (age at onset <60 yr) and 24 aged healthy subjects were analysed. RESULTS: Sixty-five per cent of EORA patients had anti-CCP Abs, whereas none of the PMR patients or the aged healthy subjects was positive for those antibodies. Ten of the EORA patients started with polymyalgic symptoms and two of them were positive for anti-CCP Abs. Interestingly, there was a significant correlation between anti-CCP Abs and RF in EORA but not in young RA patients. CONCLUSIONS: The presence of anti-CCP Abs in a patient with clinical symptoms of PMR must be interpreted as highly suggestive of EORA.     

类风湿关节炎中抗纤聚蛋白抗体意义的探讨

目的探讨抗纤聚蛋白抗体(AFA)在类风湿关节炎(RA)中的意义,并比较AFA与类风湿因子(RF)、抗角蛋白抗体(AKA)、抗核周因子(APF)和抗环瓜氨酸肽(CCP)抗体以及某些临床指标的相关性。方法对860例研究对象,包括388例RA患者(其中早期172例,中晚期216例),422例非RA的风湿性疾病患者,50名健康对照,用免疫印迹法(IB)检测血清中的AFA。同时检测其他RA相关自身抗体。结果AFA在早期RA病例中阳性率为62.2%,在中晚期RA病例中阳性率为58.8%,对RA诊断敏感性60.3%,特异性91.1%,阳性和阴性预测值分别为94.6%、68.0%。AFA和AKA在早期和中晚期RA的阳性率差异无统计学意义,而RF、APF和抗CCP抗体在中晚期组的阳性率大于早期组。AFA与RF、AKA、APF以及抗CCP抗体相关(P<0.05)。AFA与RA患者平均发病年龄相关(P=0.047)。结论AFA可视为RA的特异性血清学标记,尤其对RF阴性及早期RA诊断很有帮助;AFA与其他RA相关自身抗体相关,联合检测可以相互补充,提高对RA的诊断。     

The role of anticyclic citrullinated peptide antibodies in the differential diagnosis of elderly-onset rheumatoid arthritis and polymyalgia rheumatica

There are clinical difficulties to differentiate elderly-onset rheumatoid arthritis (EORA) patients from those with polymyalgia rheumatica (PMR), especially when dealing with EORA-like PMR-onset, seronegative EORA, and PMR with peripheral synovitis, which constitute the subgroups presenting the greatest difficulties. Serum samples were obtained from two groups of patients, one with EORA diagnosis and another with a PMR diagnosis. Anticyclic citrullinated peptide (anti-CCP) antibodies (enzyme-linked immunosorbent assay method) and rheumatoid factor (RF; latex technique) were determined. Of the 16 EORA patients, 9 presented anti-CCP antibodies, 4 of whom tested positive for RF. Of the 12 EORA patients who remained negative to RF, 5 were positive for anti-CCP antibodies. Eight of the EORA patients started with polymyalgic symptoms. Three of these patients showed positive titles of anti-CCP antibodies with negative RF. All PMR patients presented negative anti-CCP antibodies, except one with weak positive titles, and all were negative for RF. Of 15 patients with PMR, 7 presented oligoarticular synovitis at the onset. After a mean follow-up of 3 months, two patients developed RA. When evaluating them for RF and anti-CCP antibodies, one tested negative, while the other was positive for both antibodies. We observed a tendency to higher values of anti-CCP antibodies in patients with extraarticular manifestations, radiological damage, and disease-modifying antirheumatic drugs. When compared to the PMR group, EORA patients presented positive anticitrulline antibodies at the beginning of the disease in a statistically significant amount. One third of the seronegative EORA patients presented positive anti-CCP antibodies at the onset.     

抗环瓜氨酸肽抗体在类风湿关节炎诊断中的意义及对关节侵蚀预测的价值

目的研究抗环瓜氨酸肽抗体(抗CCP抗体)在类风湿关节炎(RA)诊断中的意义及与关节侵蚀的关系。方法检测84例RA患者抗CCP抗体、抗角蛋白抗体(AKA)、类风湿因子(RF),评价三者诊断RA的价值。将75例RA患者分为轻微关节侵蚀组41例(第1组)和严重关节侵蚀组34例(第2组),分析与RA关节侵蚀相关的因素。结果3种抗体诊断RA的敏感性和特异性分别为:抗CCP抗体(49%,94%)、AKA(50%,93%)、RF(79%,67%);三者两两组合后诊断RA的特异性增高。三者在第2组中的阳性率明显高于第1组(P<0.05)。抗CCP抗体阳性患者更易出现关节侵蚀(OR=6.71)。多因素分析表明抗CCP抗体、AKA、C反应蛋白(CRP)、类风湿结节与关节侵蚀有关,其中类风湿结节权重最大(OR=12.07)。结论抗CCP抗体是RA良好的诊断指标,并且与关节侵蚀密切相关。抗CCP抗体与AKA、RF联合使用可进一步提高诊断的准确性。对关节侵蚀的多种危险因素进行综合评价有助于判断RA的预后。     

Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid arthritis

OBJECTIVE: To explore the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) detected by ELISA in patients with rheumatoid arthritis (RA). METHODS: The synthesized cyclic citrullinated peptide was used as substrate for ELISA. Anti-CCP antibody was detected by ELISA in 191 patients with RA, 132 with rheumatic diseases other than RA, and 98 with nonrheumatic diseases. The antiperinuclear factor (APF), anti-keratin antibody (AKA), rheumatoid factor (RF), and HLA-DR4 gene complex were also tested in each RA patient. The results of these tests were compared with anti-CCP antibody to examine the correlation between them. RESULTS: Ninety (47.1%) patients with RA, 4 (3.0%) with other rheumatic diseases, and 2 (2.0%) with nonrheumatic diseases were found to be anti-CCP antibody positive by ELISA. The sensitivity of anti-CCP antibody was 47.1%, with a high specificity (97.4%) in RA. Anti-CCP antibody correlated with APF, AKA, RF, and HLA-DR4 gene complex. CONCLUSION: A new modified anti-CCP antibody test had a moderate sensitivity (47.1%) but a high specificity (97.4%) in patients with RA and was found as a valuable supplement to diagnosis of RA. Anti-CCP correlated with APF, AKA, RF, and HLA-DR4 gene complex, but did not completely overlap with them. Anti-CCP antibody could be regarded as a new diagnostic marker for RA.     

四种抗体联合检测在类风湿关节炎早期诊断中的应用价值

目的 探讨抗核周因子抗体(APF)、抗角蛋白抗体(AKA)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗-CCP抗体)联合检测在类风湿关节炎(RA)早期诊断中的临床应用价值。方法 对RA患者127例、非RA其他风湿病患者102例及正常对照组43例，采用速率散射免疫比浊法检测RF；酶联免疫吸附法定量检测抗-CCP抗体；免疫荧光法检测AKA、APF，并采用四格表法计算敏感度及特异性。结果RA组的RF、APF、AKA、抗-CCP抗体敏感度分别为65．4％、48．8％、32．3％、83．5％，特异性分别为73．5％、92．2％、93．1％、94．1％，同时出现三种抗体和四种抗体的特异性为99．0％、100％；非RA组无四种抗体同时出现的情况。结论 RF敏感性较高，但特异性较差；APF、AKA、抗-CCP抗体三种自身抗体对RA具有高度特异性，且在RA早期即可出现。四种抗体联合检测有助于提高RA的早期诊断率。     

Anti-CCP and antikeratin antibodies in rheumatoid arthritis, primary Sjögren’s syndrome, and Wegener’s granulomatosis

The objective of this study was to investigate the frequency of antibodies against cyclic citrullinated peptides (anti-CCP) and keratin (AKA) in patients with rheumatoid arthritis (RA) as well as in patients with primary Sjögrens syndrome (pSS) and Wegeners granulomatosis (WG), who may present with rheumatoid factor (RF)-positive arthritis. The study group consisted of 46 patients with RA (26 patients were negative for RF), 32 with pSS, 22 with WG, and 40 healthy controls. The RF, anti-CCP, and AKA were detected in serum using the latex agglutination test, enzyme-linked immunosorbent assay, and indirect immunofluorescence, respectively. The agreement between those tests was evaluated by kappa test. No positive result for AKA was detected in pSS and WG patients, and anti-CCP was found in only one patient with pSS. The results of kappa tests were low, varying between 0.25 (RF-anti-CCP) and 0.02 (RF-AKA). The sensitivity and specificity values were 43 and 44% for RF, 65 and 98% for anti-CCP, and 58 and 100% for AKA, respectively, in RA patients. In the RF-negative RA group, AKA was found to have a high frequency (55%) in comparison to anti-CCP (38%). Seropositivity was found to be 87% for any one of the three autoantibodies tested in RA patients. With a higher specificity, values for RA, anti-CCP, and AKA seem to be helpful for the differential diagnosis of patients with RF-positive arthritis, which may include patients with WG and pSS, and screening of all three antibodies may increase the diagnostic performance.