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.     

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。     

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。     

抗环瓜氨酸多肽抗体检测早期诊断类风湿关节炎研究

目的探讨抗环瓜氨酸多肽(CCP)抗体检测对类风湿关节炎(RA)早期诊断的意义。方法应用ELISA法检测2004—2005年中国医科大学附属盛京医院150份人血清的抗CCP抗体,包括54例RA患者,80例其它风湿病患者,16名正常人;并分析抗CCP抗体与类风湿因子(RF)、C反应蛋白(CRP)、血沉(ESR)的相关性。结果抗CCP抗体对RA的敏感性和特异性分别为70·4%和93·8%。发病2年内与2年以上的抗CCP抗体阳性率差异无显著性。抗CCP抗体阴性组与阳性组的关节畸形率差异无显著性。抗CCP抗体与RF、CRP、ESR无相关性。结论抗CCP抗体对RA具有较好的敏感性和很高的特异性,联合抗CCP抗体和RF可以提高诊断的准确性,对RA的早期诊断具有重要意义。     

抗角蛋白抗体在类风湿关节炎的临床意义

目的研究抗角蛋白抗体(AKA)在类风湿关节炎(RA)的临床意义。方法98例RA患者及70例其他风湿性疾病患者测定血清抗角蛋白抗体,对两组病人AKA阳性率进行比较,并对抗角蛋白抗体与类风湿因子(RF)对RA诊断的敏感性和特异性进行比较,同时对RA患者AKA阳性组和AKA阴性组的关节肿胀指数、关节压痛指数、握力、晨僵时间、休息痛和RF、血沉、C反应蛋白、影像学检查以及关节外表现等临床指标进行比较,对资料进行统计分析。结果RA患者AKA阳性率明显高于其他风湿性疾病患者(P<0.001);AKA对于RA诊断较RF更具特异性;RA患者中AKA阳性组较AKA阴性组病情严重,除握力外各项观察指标比较均有统计学意义(P<0.05)。结论AKA检测对RA诊断、病情预测和指导治疗均有较高的临床价值。     

自身抗体阳性的未分化关节炎向类风湿关节炎转化的预测价值

目的 探讨类风湿因子(RF)、抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体、抗核周因子(APF)4种自身抗体对未分化关节炎(UA)转化为类风湿关节炎(RA)的临床预测价值,并分析其临床相关因素.方法 对271例UA患者随访1年,采用免疫比浊法检测RF,酶联免疫吸附试验(ELISA)检测抗CCP抗体,间接免疫荧光法(IIF)检测APF与AKA,魏氏法测定红细胞沉降率(ESR),记录患者的晨僵时间、关节肿胀数、关节压痛数、不同关节受累及DAS28评分.结果 4种抗体均阳性的UA患者转化为RA的阳性率为99%;任2种及2种以上抗体阳件的UA患者转化为RA的敏感性83.0%,特异性65.9%;RF/抗CCP抗体阳性的UA患者转化为RA的敏感性77.8%,特异性80.5%;抗体均阴性和任1、2、3种抗体阳性及4种抗体全阳性患者的多关节肿胀及多个小关节受累的比率分别为48%、57%、59%、70%、70%和71%、71%、72%、76%、82%;抗体阴性的UA患者中肘关节受累所占比例最大,为72%;多关节肿胀及多个小关节受累在UA转化为RA与无多关节肿胀及多个小关节受累的转化率最大.结论 4种抗体联合检测可提高RA早期诊断的特异性,阳性抗体越多.UA越容易发展为RA;RF/抗CCP抗体阳性的UA患者转化为RA的敏感性和特异性均较高.多关节肿胀和多个小关节受累对评估RA病情有重大意义.     

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。     

三种抗体对老年类风湿关节炎患者的诊断作用比较

<正>目前在类风湿关节炎(RA)的诊断标准中,类风湿因子(RF)是唯一的血清学指标,但由于RF特异性低,早期检出率不高,给RA的诊断特别是早期诊断带来难度。目前瓜氨酸相关自身抗体系统中抗角蛋白抗体(AKA)对RA诊断具有高特异性〔1,2〕,以环瓜氨酸肽(CCP)为抗原的酶联免疫吸附试验(ELISA)更显示出在RA诊断中具有高度特异性〔3,4〕。本研究探讨血清中的抗CCP、RF、AKA抗体在RA临床诊断中的价值。     

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。     

抗环瓜氨酸肽抗体与类风湿关节炎疾病活动及骨侵蚀关系的研究

目的 探讨类风湿关节炎(RA)患者抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)与疾病活动度、功能状态及骨侵蚀的关系.方法 入选RA患者218例.健康对照41名,ELISA法检测抗CCP抗体,乳胶凝集法检测RF,同时记录RA患者的临床资料.分析抗CCP抗体、RF阳性和阴性患者中疾病活动指数28(DAS28)、健康评估问卷(HAQ)的变化,并探讨其中124例病程>2年的患者抗CCP抗体、RF与骨侵蚀的关系.结果 RA患者中抗CCP抗体阳性率为76%,RF阳性率为71%.DAS28评分在抗CCP抗体、RF阳性患者明显高于阴性患者(P＜0.05);抗CCP抗体浓度与DAS28评分相关(r=0.385,P=0.032);RF滴度与DAS28评分相关(r=0.141,P=0.037);红细胞沉降率(ESR)、C反应蛋白(CRP)及HAQ评分在抗CCP抗体、RF阳性和阴性患者之间的差异无统计学意义(P＞0.05).抗CCP抗体阳性患者更易出现骨侵蚀,与阴性患者相比,差异有统计学意义(P＜0.05).RF阳性和阴性患者之间骨侵蚀的差异无统计学意义.结论 抗CCP抗体、RF与疾病活动度相关,抗CCP抗体阳性患者更易出现骨侵蚀,但RF与骨侵蚀未表现出相关性.     

Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage

OBJECTIVE: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). METHODS: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. RESULTS: Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. CONCLUSION: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.     

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。     

Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis

OBJECTIVE: To compare the diagnostic values of antiperinuclear factor (APF), antikeratin antibody (AKA), and anti-cyclic citrullinated peptides (anti-CCP) to discriminate between patients with and without rheumatoid arthritis (RA) and to determine the diagnostic value of anti-CCP used alone or with other tests. METHODS: Two hundred and seventy patients with early arthritis underwent standardized investigations in 1995-1997. The clinical utility of APF, AKA, and anti-CCP in first-visit sera was evaluated using receiver-operating characteristic curves. Combinations of anti-CCP with other laboratory tests were assessed by multiple logistic regression. RESULTS: Anti-CCP, APF, and AKA were not perfectly correlated with one another. Anti-CCP with 53 UI as the cutoff was 47% sensitive and 93% specific, versus 52% and 79%, and 47% and 94%, for APF and AKA, respectively. Multiple logistic regression selected anti-CCP, AKA, IgM-rheumatoid factor (RF) ELISA, and the latex test. CONCLUSION: Rheumatologists can routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and either AKA or anti-CCP ELISA) and can add a third or fourth test when the diagnosis remains in doubt.     

Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA

Introduction: Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity. Materials and methods: A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at −70°C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean±2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive. Results: The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05). Conclusion: Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.     

The association of anti-CCP antibodies with disease activity in rheumatoid arthritis

Antibodies to citrullinated proteins have been described in patients with rheumatoid arthritis (RA) and these appear to be the most specific markers of the disease. Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in patients with RA and the association of anti-CCP antibodies with disease activity, radiological erosions and HLA DR genotype. Forty patients with RA and 38 patients with fibromyalgia were included in this study. Serum samples were collected from both patient groups with RA and fibromyalgia. Anti-CCP was measured by the corresponding enzyme-linked immunosorbent assay. Additionally, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score (DAS), visual analog scala (VAS), HLA genotype and radiographic information were determined in patients with RA. The rate of sensitivity and specificity of anti-CCP reactivity for the diagnosis RA were measured (sensitivity 50%, specificity 100%). There is no significant difference between anti-CCP (+) and anti-CCP (-) RA patients for DAS28, VAS, ESR, CRP, disease duration, HLA genotype, and radiological assessment of hand. However, there was a significant difference between anti-CCP (+) and anti-CCP (-) RA patients for RF and the radiological assessment of left and right wrists (respectively, P < 0.05, P = 0.04, P = 0.01). There was no significant correlation between anti-CCP antibody and ESR, CRP, VAS, DAS 28 or radiological assessment. A small but significant correlation was found between RF and anti-CCP antibody (P = 0.02, r = 0.35).     

Second generation anti-cyclic citrullinated peptide (anti-CCP2) antibodies can replace other anti-filaggrin antibodies and improve rheumatoid arthritis diagnosis

We compared the diagnostic performance of anti-cyclic citrullinated peptide antibodies detected with second-generation enzyme immunoassay (anti-CCP2) with that of IgM-rheumatoid factor (RF), anti-perinuclear factor (APF), and anti-keratin antibodies (AKA). The sensitivity of anti-CCP2 was better than that of APF and AKA: they were detected in 25% rheumatoid arthritis (RA) patients without detectable APF or AKA. Their specificity, evaluated in other inflammatory rheumatic disease, was similar to that of APF and AKA. Despite the lower specificity, IgM-RF in combination with anti-CCP2 is interesting, as they do not completely overlap. Anti-CCP2 antibody detection seems to be a good alternative to other anti-filaggrin antibodies in the diagnosis of RA.     

Anti-cyclic citrullinated peptide antibodies as a discriminating marker between rheumatoid arthritis and chronic hepatitis C-related polyarthropathy

Articular involvement is a frequent extrahepatic manifestation of hepatitis C virus (HCV) infection. The distinction between HCV-related polyarthropathy and true RA may be very difficult, especially with recent onset RA before articular damage and erosions develop. The objective of the study is to assess the diagnostic utility of anti-CCP antibodies and compare it with that of rheumatoid factor (RF) in distinguishing between rheumatoid arthritis (RA) and HCV-related polyarthropathy. Anti-cyclic citrullinated peptide (CCP) antibodies and RF were determined in the sera of 30 patients with RA and 22 patients with HCV-related polyarthropathy. Anti-CCP antibodies were positive in 83.3% of patients with RA and in 4.5% in patients with HCV and polyarthropathy. RF was positive in 90% of RA patients and in 81.1% of HCV patients with polyarthropathy. The anti-CCP antibodies showed higher specificity for RA compared with RF (95.4 vs. 18.2%). However, the sensitivity of anti-CCP was comparable to that of RF (83.3 vs. 90%). In conclusions, anti-CCP antibodies are reliable laboratory markers to differentiate between RA and HCV-related polyarthropathy.