抗角蛋白抗体、抗核周因子及类风湿因子对类风湿关节炎的诊断意义

抗角蛋白抗体、抗核周因子及类风湿因子对类风湿关节炎的诊断意义张江林施桂英黄烽丁玉珍孟庆功徐明类风湿关节炎（ＲＡ）特异的诊断标记一直是研究的热点，国外的研究表明抗角蛋白抗体（ＡＫＡ）、抗核周因子（ＡＰＦ）和类风湿因子（ＲＦ）在ＲＡ具有诊断意义［１］。本...     

类风湿关节炎血清学早期诊断

目的 探索抗核周因子（ＡＰＦ）、抗角蛋白抗体（ＡＫＡ）、抗Ｓａ抗体及抗ＲＡ３３／３６抗体检测对ＲＡ的早期诊断价值。方法 对未肯定诊断的关节痛／关节炎病人１１６例进行上述四种抗体检测并随访观察。ＡＰＦ和ＡＫＡ用间接免疫荧光法进行检测。抗Ｓａ抗体和抗ＲＡ３３／３６抗体用免疫印迹法检测。结果 对１１６例未肯定诊断的关节痛／关节患者随访４￣１８个月。ＡＰＦ阳性的２９例中,最后确诊为ＲＡ２０（６９％）;ＡＫ     

HLA—DR4基因检测在类风湿关节炎诊治中的意义探讨

为了研究ＨＬＡ－ＤＲ４基因检测在类风湿关节为诊治中的意义，对５０例类风湿关节炎患者进行了ＨＬＡ－ＤＲ４的（ＰＣＲ－ＳＳＰ方法）检测，同时结合患者的临床表现和实验室指标进行分析。结果显示：ＨＬＡ－ＤＲ４阳性者３１例（阳性率为６２％）；比较ＨＬＡ－ＤＲ４阳性和阴性两组患者其他指数，可见，ＩＨＬＡ－ＤＲ４阳性组的关节疼痛指数、ＥＳＲ、类风湿因子（ＲＦ）滴度均明显高于ＨＬＡ－ＤＲ４阴性组（Ｐ值分别〈０．０     

强直性脊柱炎合并类风湿关节炎

目的：分析强直性脊柱炎（ＡＳ）合并类风湿关节炎（ＲＡ）患者的临床特点。方法：自１９８８年－１９９７年我科临床中共诊断ＡＳ合并ＲＡ患者２０例，通过与单纯ＡＳ（６５例）和ＲＡ（４６例）比较其特点。结果：通过比较发现ＡＳ合并ＲＡ患者病情活动指标高，骨质损害重。类风湿因子（ＲＦ）阳性率为６０％（１２／３０），ＨＬＡ－Ｂ２７例抗原阳性率为５８．９％（１１／１９），二者同时阳性率为５１．２％（８／１９），明显     

抗肺炎克雷白杆菌亚单位抗体与强直性脊柱炎

以免疫印迹法（Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ）测定２６例强直性脊柱炎（ＡＳ）患者和７例类风湿关节炎（ＲＡ）病人及正常人抗肺炎克雷白杆菌（ＫＰ）抗体阳性血清中抗ＫＰ亚单位抗体。结果表明，ＡＳ患者血清抗ＫＰ亚单位抗体阳性区带条数为６．６±１．９条，ＲＡ患者和正常人为３．６±１．３条（Ｐ＜０．０５）。ＡＳ患者血清抗ＫＰ亚单位抗体以６４６００，４８２００以及３６０００抗体占多数，阳性率分别为８０．７％，６１．５％和６５．４％；ＲＡ患者和正常人血清则以抗３６０００和３００００亚单位抗体占多数，阳性率分别为７５％和５０％。抗ＨＬＡ－Ｂ＿（２７）单价血清和兔抗人工合成１８肽（含与ＨＬＡ－Ｂ＿（２７）相同氨基酸序列片段）抗血清能与ＫＰ抗原中的６４６００和４８２００两个亚单位分子起交叉反应，提示这两个亚单位分子与ＨＬＡ－Ｂ＿（２７）有共同的抗原成分，推测ＫＰ感染可能通过与ＨＬＡ－Ｂ＿（２７）的分子模拟在ＡＳ的发病中起作用。     

抗Sa抗体的检测及其临床意义

目的 了解抗Ｓａ抗体的临床意义。方法 从新鲜人胎盘中提取Ｓａ抗原,应用免疫印迹法检测类风湿关节炎（ＲＡ）及其他风湿病患者血清的抗Ｓａ抗体,结合临床资料进行分析。结果 １９２例ＲＡ中抗Ｓａ抗体阳性６５例,对ＲＡ诊断的敏感性为３３．９％,特异性为９６．９％。其中同时出现相对分子量为５００００、５５０００两条带的１５例（２３．１％）,其工程师和患者对病情活动性的评价、患者对关节痛的评价及Ｃ反应蛋白（ＣＲ     

血小板自身抗体的流式细胞仪检测与意义

目的：应用流式细胞术（ＦＣＭ）测定血小板自身抗体ＰＡＩｇＧ,研究其对待发性血小板减少性紫癜（ＩＴＰ）诊断的意义。方法：应用ＦＣＭ检测２０例ＩＴＰ患者血小板膜表面及血浆中的抗血小板抗体,并与ＥＬＩＳＡ所测结果进行比较。结果：ＦＣＭ测得１４例（７０％ＩＴＰ患者血小板膜自身抗体ＰＡＩｇＧ阳性,９例（４５％）血浆抗血小板抗体阳性。ＥＬＩＳＡ显示１２例（６０％）患者ＰＡＩｇＧ阳性,７例（３５％）血浆抗血小板     

抗Sa抗体在类风湿关节炎中的意义

目的测定自身免疫性结缔组织病中抗Ｓａ抗体的阳性率，着重分析抗Ｓａ抗体在类风湿关节炎（ＲＡ）中的意义。方法从人胎盘中提取Ｓａ抗原，采用免疫印迹法，测定了４０例健康人及４７８例各种自身免疫性结缔组织病患者血清中的抗Ｓａ抗体，并分析了该抗体与ＲＡ的某些临床及实验室指标的相关性。结果抗Ｓａ抗体在各组患者中的阳性率分别为：ＲＡ为３１．９％（６１／１９１），干燥综合征为３．０％（２／６７），系统性红斑狼疮为４．３％（２／４６），白塞病、肌炎／皮肌炎、其他自身免疫性结缔组织病及正常人中均为０。研究分析表明，抗Ｓａ抗体对ＲＡ的诊断敏感性为３１．９％，特异性为９８７％，阳性预报率为９３．８％，阴性预报率为７１．３％。与抗Ｓａ抗体阴性的ＲＡ患者相比，抗Ｓａ抗体阳性的患者在关节受累、晨僵、血沉、抗核抗体、Ｘ线分期和二线药物的使用方面有显著差异。结论我们在国内首次制备了Ｓａ抗原，并建立了Ｓａ抗体的检测方法，它是一种不同于类风湿因子、对ＲＡ诊断较为特异的新型自身抗体。该抗体与疾病的严重程度相关，能否有助于ＲＡ的早期诊断和分型尚需更多病例的积累和观察。     

类风湿关节炎患者胃肠损害与幽门螺杆菌感染的相关性研究

目的 探讨Ｈｐ在类风湿关节炎（ＲＡ）患者胃肠损害中可能发挥的作用。方法 以１６例强直性脊柱炎（ＡＳ）及１１例行发性消化道溃疡（ＰＵＤ）患者为对照,对４６例ＲＡ患者进行胃镜检查,并采集胃窦粘膜组织进行Ｗａｒｔｈｉｎ－Ｓｔａｒｒｙ银染色及ＰＣＲ扩增法,同时应用ＥＬＩＳＡ法测定患者血清抗Ｈｐ－ＩｇＧ抗体水平,综合判定Ｈｐ感染状态。统计ＲＡ患者Ｈｐ感染与胃镜下改变及临床指标的相关性。并对ＲＡ患者作胃肠道溃     

类风湿关节炎患者进行血清与滑液抗组蛋白抗体检测的临床意义

类风湿关节炎患者进行血清与滑液抗组蛋白抗体检测的临床意义济南军区总医院（２５００３１）陈常胜，张伟解放军总医院施桂英本文以酶联免疫吸附试验（ＥＬＩＳＡ）对２０例类风湿关节炎（ＲＡ）患者分别进行血清及滑液抗组蛋白抗体（ＡＨＡ）检测，并探讨其临床意义。１...     

老年类风湿关节炎患者抗角蛋白抗体检测意义

目的：了解抗角蛋白抗体（AKA）对老年类风湿关节炎（EORA）的诊断意义。方法：以Wistar大鼠中1／3食管组织冰冻切片为底物，采用间接免疫荧光光检测51例EORA及139例对照组的血清AKA，记录同期临床及实验室指标。结果：AKA对EORA诊断敏感性为31．4％，特异性为98．6％，早期EORA患者AKA阳性率28．6％，AKA阳性组IgM、血沉（ESR）较阴性组高；医生及患者对病情活动性评分、Sharp评分有增高趋势。16例AKA阳性EORA中，类风湿因子（RF）、抗核周因子（APF）、抗Sa抗体阳性数分别为11、15例和4例，AKA和APF相关。结论：AKA有助于EORA诊断及早期诊断，是病情活动性及严重性指标。     

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.     

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.     

Clinical relevance of antikeratin antibodies in rheumatoid arthritis

Summary Antikeratin antibodies (AKA) were found in 38 out of 96 patients with rheumatoid arthritis (RA); they appeared to be quite characteristic to this disease. There was a very low incidence of AKA positivity in the control groups, i.e., 1 out of 62 healthy subjects and 4 out of 158 other patients. With regard to the sensitivity of the test as a diagnostic tool, AKA was found to be weaker than the rheumatoid factor (RF) and the antiperinuclear factor (APF), whereas the specificity was much better than APF and RF. A clear correlation was shown between the titres of AKA and APF (p<0.001) and also between AKA levels and inflammation (p<0.02).     

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。     

An eight year prospective study of outcome prediction by antiperinuclear factor and antikeratin antibodies at onset of rheumatoid arthritis

OBJECTIVES: Antikeratin antibodies (AKA) and antiperinuclear factor (APF) are specific antibodies found very early in rheumatoid arthritis (RA). The objective of this eight year follow up study was to assess the value of early AKA and APF assays in predicting functional disability and cartilage damage. METHOD: In 2000, 64 patients tested for AKA and APF (antifilaggrin antibodies) between 1990 and 1993 during evaluation of early symmetric oligoarthritis or polyarthritis (suspected RA) were invited to participate in this non-concurrent cohort study. The Health Assessment Questionnaire (HAQ) score, disease activity score (DAS), and Larsen radiographic score were the primary evaluation criteria. RESULTS: Twenty nine patients were re-evaluated. Clinical and laboratory data obtained in 1993 were similar in this group and in the 35 other patients. Twenty five patients had received a diagnosis of RA. Nine (31%) were rheumatoid factor (RF) positive, nine (31%) were AKA positive, and six (21%) were APF positive during the first year of the disease. APF was correlated with the Larsen score (p=0.011) and DAS (p=0.035) evaluated after a mean disease duration of 8.55 years. All APF positive patients had erosive disease. AKA was correlated with the DAS (p=0.035). CONCLUSION: The presence of AKA or APF early in the course of RA was associated with the DAS or Larsen score eight years later. The number of patients was small, but the findings confirmed those of studies with shorter follow ups. Antifilaggrin antibodies should be included in the initial investigation of patients with RA and, when positive, should alert to a high risk of poor outcomes.     

抗环瓜氨酸肽抗体检测在类风湿关节炎中的意义

目的 检测抗环瓜氨酸肽（CCP）抗体在类风湿关节炎（RA）中的阳性率,探讨抗CCP抗体检测在RA中的意义。方法 以根据已知cDNA序列人工合成的CCP为抗原建立ELISA方法检测294例RA,132例其他风湿性疾病,135例非风湿性疾病中的抗CCP抗体的分布。比较抗CCP抗体与抗核周因子（APF）、抗角蛋白抗体（AKA）、类风湿因子（RF）以及HLA－DR4的相关性。结果 294例RA病人中,抗CCP抗体的阳性率为46．6％,其他风湿性疾病的阳性率为5．3％,非风湿性疾病的阳性率为1．5％。抗CCP抗体对RA的敏感性和特异性分别为46．6％,96．6％。抗CCP抗体与APF、AKA以及HLA－DR4之间有相关性,与RF之间无相关性。结论 抗CCP抗体对RA具有良好的敏感性（46．6％）和特异性（96．6％）,能用于RA的诊断。抗CCP抗体与AFP、AKA有相关性,但不完全重叠。抗CCP抗体可视为RA新的血清学诊断指标。     

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.     

血清高迁移率族蛋白1水平与类风湿关节炎临床指标的相关性

目的通过检测活动性类风湿关节炎(rheumatoid arthritis,RA)患者血清高迁移率族蛋白1(high mobility group box protein 1,HMGB1)表达水平,探讨HMGB1与RA患者疾病活动性、自身抗体及临床指标的相关性。方法采用双抗体夹心酶联免疫吸附试验测定67例活动性RA患者和21位健康对照者血清HMGB1水平。收集RA患者的同期临床资料并测定相关实验室指标:疼痛视觉模拟评分(visual analog scale,VAS)、疲乏VAS、肿胀关节数、压痛关节数、患者对疾病总体状况的VAS(patient′s global assessment,PGA)、健康评估问卷(health assessment questionnaire,HAQ)、疾病活动评分28(dise aseactivity score28,DAS28)、血沉、C-反应蛋白、类风湿因子-IgM、抗环瓜氨酸肽抗体等,分析以上指标与血清HMGB1的相关性。结果活动性RA组血清HMGB1中位数为8.7ng/ml,四分位间距为16.59ng/ml;健康对照组血清HMGB1中位数为3.47ng/ml,四分位间距为7.43ng/ml,活动性RA组血清HMGB1表达水平显著高于健康对照组,两组间比较差异有统计学意义(P0.01)。活动性RA患者血清HMGB1表达水平与类风湿因子呈正相关(P0.01),与疼痛VAS评分、疲乏VAS评分、肿胀关节数、压痛关节数、PGA、HAQ、DAS28评分及血沉、C-反应蛋白、抗环瓜氨酸肽抗体无相关性(P0.05)。结论活动性RA患者血清HMGB1表达水平较健康对照组显著升高,但可能与疾病活动无关。     

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.