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.     

类风湿关节炎患者抗环瓜氨酸肽抗体与人类白细胞抗原-DR4等位基因相关性研究

目的 研究类风湿关节炎(RA)及未分类关节炎(痛)(UA)患者抗环瓜氨酸肽(CCP)抗体与人类白细胞抗原(HLA)-DR4等位基因相关性.方法 对91例RA患者,46例UA患者,35名健康志愿者,均为浙江汉族人,应用酶联免疫吸附试验(ELISA)法检测血清抗CCP抗体,序列特异性引物聚合酶链反应(PCR-SSP)检测HLA-DR4等位基因.结果 RA组、UA组HLA-DR4阳性率分别为47.2%、45.6%,均以DRB1*0405为主,分别为25.3%、23.9%.RA组、UA组患者的抗CCP抗体与HLA-DR4具有相关性(r=613,0.703,P＜0.01).与HLA-DRB1*0405具有弱相关性(r=0.304,P＜0.01;r=0.333,P＜0.05). 2组HLA-DR4阳性患者抗CCP抗体水平明显高于HLA-DR4阴性患者,差异有统计学意义(P＜0.01).抗CCP抗体、HLA-DR4均阳性患者红细胞沉降率(ESR)、C反应蛋白(CRP)、血小板水平明显升高,晨僵时间延长,关节肿胀度积分升高,与二者阴性患者比较,差异有统计学意义(P＜0.05或P＜0.01).对UA组患者3个月后随访,抗CCP抗体、HLA-DR4在早期RA的阳性率为94.7%(18/19).结论 抗CCP抗体与HLADR4、DRB1*0405相关;抗CCP抗体、HLA-DR4均阳性反映了RA病情活动性;联合检测抗CCP抗体、HLA-DR4或DRB1*0405有助于RA早期诊断;抗CCP抗体可能在HLA-DR4等遗传因素参与下介导了RA发病.     

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.     

血清抗CCP抗体、抗RA33抗体在类风湿关节炎诊断中的价值

检测75例类风湿关节炎(RA)患者(RA组)、54例非RA风湿病患者(非RA组)及40例健康人(对照组)血清中抗环瓜氨酸肽(CCP)抗体(简称抗CCP)、抗RA33抗体(简称抗RA33)水平,并与类风湿因子(RF)比较.结果RA组抗CCP、抗RA33和RF的阳性率及滴度均明显高于其他两组;抗CCP、抗RA33对RA的敏感性较RF低,特异性较RF高.抗CCP与RF诊断一致性好,抗RA33与RF诊断一致性差.认为抗CCP和抗RA33有助于不典型RA(特别是RF阴性的RA)的诊断,在一定程度上可弥补RF对RA诊断不足.三种抗体联合检测可提高RA的诊断率.     

Ⅰ型胶原吡啶交联终肽及抗环瓜氨酸肽抗体等联合检测在类风湿关节炎诊断与病情监测中的应用

目的 探讨Ⅰ型胶原吡啶交联终肽(Ⅰ CTP)、抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)、C-反应蛋白(CRP)检测在类风湿关节炎(RA)诊断与病情监测中的应用.方法 2006年4月至10月对南昌大学第一附属医院住院及门诊RA患者57例(RA组)、非RA的其他风湿免疫系统疾病患者25例(非RA对照组)及健康对照(健康对照组)30名,采用ELISA定量检测测定血清Ⅰ CTP、抗CCP抗体,采用免疫散射比浊法测定血清RF、CRP.结果 (1)RF、CRP、Ⅰ CTP及抗CCP抗体在健康对照组、非RA对照组、RA活动组及缓解稳定组间差异均有显著性意义(P＜0.01),其中抗CCP抗体、RF、CRP在RA活动组中的浓度均高于其他组,而在健康对照组、RA缓解稳定组及非RA对照组间差异均无显著性意义(P＞0.05);血清Ⅰ CTP在RA活动组中的浓度高于RA缓解稳定组与健康对照组,而RA缓解稳定组与健康对照组间差异无显著性意义(P＞0.05).(2)RA组RF、抗CCP抗体、Ⅰ CTP、CRP的阳性率分别为73.7%,52.6%,61.4%,56.1%.(3)Ⅰ CTP与抗CCP抗体、RF、CRP,抗CCP抗体与RF、CRP及RF与CRP在RA组中均呈正相关(rs=0.474,0.366,0.645,0.536,0.643,0.555,P均＜0.05),且定性结果相关性显著(P均＜0.01);在非RA对照组中无相关(P均＞0.05).(4)RF和抗CCP抗体的联合敏感度为87.5%,联合特异度为49.9%.结论 联合检测抗CCP抗体与RF可降低RA的漏诊率.动态联合测定ⅠCTP、抗CCP抗体、RF、CRP能更有效地及时监测RA的疾病进展,对指导临床诊治及干预有积极意义.     

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。     

儿童系统性红斑狼疮抗环瓜氨酸肽抗体检测及其临床意义

目的 检测儿童系统性红斑狼疮(JSLE)患者血清抗环瓜氨酸肽(CCP)抗体水平,了解抗CCP抗体在该病中的阳性检出率以及探讨其与关节炎表现相关性.方法 采用第3代抗CCP抗体酶联免疫吸附试验(ELISA)检测47例JSLE、54例幼年特发性关节炎(JIA)患者和40名年龄匹配的健康儿童血清中抗CCP抗体水平,并分析该抗体与JSLE实验室指标及临床特征,尤其是关节表现之间关系.正态分布的计量资料比较采用t检验,非正态资料比较采用Mann-Whitney U检验,率的比较采用χ2或Fisher精确检验.结果 47例JSLE患儿中6例为抗CCP抗体阳性,抗体阳性率明显高于健康对照组(13%与0,P＜0.05),与JIA组(26%)差异无统计学意义(P=0.098).抗CCP抗体阳性JSLE患儿中类风湿因子(RF)阳性率显著高于阴性患者(83%与15%,P＜0.01),在其他实验室指标和包含关节炎发生率等临床特征方面差异均无统计学意义(67%与51%,P＞0.05).47例JSLE患儿中以关节炎起病者25例,无一例出现关节畸形或影像学改变,关节受累与未受累者间抗CCP抗体水平及阳性率比较差异均无统计学意义(16%与9%,P＞0.05);3例在长达3年病程中始终伴有关节疼痛、活动受限患儿抗CCP抗体均呈阴性.结论 抗CCP抗体可在系统性红斑狼疮患儿血清中检出,在同JIA作鉴别诊断时应引起重视,但抗CCP抗体与JSLE关节炎发生、持续并无明显联系.     

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。     

系统性红斑狼疮患者抗核糖体P0蛋白抗体的临床意义

目的 探讨系统性红斑狼疮(SLE)患者抗核糖体P0蛋白抗体的临床意义.方法 采用线性免疫分析法和免疫印迹法检测49例SLE患者及61例其他结缔组织病患者血清抗P0抗体和抗核糖体抗体(rRNP),分析抗P0抗体与rRNP抗体在SLE和其他结缔组织病中阳性率的差异及抗P0抗体与SLE临床表现和其他自身抗体的关系.结果 SLE患者中抗P0抗体的阳性率为36.7%,rRNP抗体的阳性率为6.1%,二者之间差异有统计学意义(P＜0.01);抗P0抗体在其他结缔组织病中均为阴性.在SLE患者中,抗P0抗体阳性组皮疹的发生率为77.8%,阴性组为35.5%(P＜0.05);抗SmD1抗体的阳性率在抗P0抗体阳性组中为61.1%,在阴性组中为19.4%(P＜0.01).抗P0抗体对诊断SLE的敏感性为36.73%,特异性为100%,阳性预测值为100%,阴性预测值为66.30%.结论 抗P0抗体对诊断SLE的特异性强,阳性预测值高.抗P0抗体与SLE皮疹和抗SmDl抗体阳性相关.     

白细胞介素-33的测定及其与早期类风湿关节炎相关性的研究

目的 通过检测早期类风湿关节炎(RA)患者血清中的白细胞介素(IL)-33水平,分析其与早期RA之间的相关性.方法 收集病程<1年的早期RA患者100例,骨关节炎(OA)患者40例以及健康对照者70名.采用双抗体夹心酶联免疫吸附试验(ELISA)测定血清中的IL-33水平,并分析血清IL-33水平与RA各临床和实验室指标的相关性.计量资料的比较采用Kruskal-Wallis检验和(或)Mann-Whitney U检验,计数资料比较采用X2检验,相关性分析采用Spearman相关分析.结果 RA患者血清IL-33水平为(282±871)pg/ml,显著高于健康对照组[(7±38)pg/ml,P(0.01)和OA患者[(8±35)pg/ml,P<0.01].血清IL-33水平与类风湿因子(RF)、隐性类风湿因子IgG(HRF-IgG)、抗环瓜氨酸肽(CCP)抗体、抗突变型瓜氨酸化波形蛋白(MCV)抗体呈正相关(r分别为:0.312,0.277,0.213,0.302,P<0.01或P<0.05). IL-33阳性组患者的RF阳性率、HRF-IgG阳性率、抗CCP抗体阳性率、抗MCV抗体阳性率(86%、31%、86%、94%)较IL-33阴性组患者(54%、11%、42%、72%)显著升高(P均<0.05). 结论 IL-33在RA患者血清中显著升高,并与多种自身抗体(包括RF、抗CCP抗体、抗MCV抗体和HRF-IgG)显著相关,可能是RA预后不良的因素之一.     

Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis

OBJECTIVES: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) can both present with an erosive arthritis with the small joints of the hands affected. Therefore a serological marker would be useful to distinguish between these two diseases at onset. In this study anti-RA33 antibodies, which are found in patients with SLE and RA, and anti-citrullinated peptide antibodies (anti-CCP), which have recently been described as highly specific for RA, were assessed. METHODS: Two hundred and thirty one patients receiving long term follow up for SLE were evaluated for arthritis and classified as erosive and non-erosive disease. Sixty six patients were tested for anti-RA33 and anti-CCP antibodies. All the patients were tested for rheumatoid factor (RF) and HLA-DR4 status. RESULTS: Ten patients had erosive disease, six of whom were RF positive (60%), and six anti-RA33 positive (60%), whereas only two were anti-CCP positive (20%). Two hundred and twenty one patients had non-erosive disease, 40 of whom were RF positive (18%), 14 were anti-RA33 positive (6%), whereas only one patient was found to be anti-CCP positive (0.5%). CONCLUSION: The presence of anti-CCP antibodies may be useful in distinguishing RA from erosive SLE. Anti-RA33 antibodies and RF are unhelpful.     

Diagnostic accuracy of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

OBJECTIVE: To correlate serum anti-cyclic citrullinated peptide antibodies (anti-CCP) levels with juvenile idiopathic arthritis (JIA) subtypes and with an erosive disease course. METHODS: The study group comprised 122 children with JIA; 16 were evaluated during both active disease and remission. Nineteen children with systemic lupus erythematosus (SLE), 27 with rheumatoid arthritis (RA), and 15 healthy children were also included in the study. Twelve children with JIA were rheumatoid factor (RF) positive, and 34 patients had persistent erosive joint disease. Anti-CCP antibody levels were determined by ELISA; values above 5 relative units were regarded as positive. RESULTS: Three girls with seropositive polyarticular JIA and erosive joint disease had positive anti-CCP values. Children evaluated during active disease and remission, patients with SLE, and healthy children all had negative anti-CCP antibody levels. However, 19/27 (70%) adult patients with RA had positive anti-CCP antibody values. CONCLUSIONS: In contrast with RA, anti-CCP positivity is only rarely found in patients with JIA. In patients with RF positivity and/or in patients with erosive joint disease, anti-CCP can be detected.     

Erosive arthropathy: clinical variance in lupus erythematosus and association with anti-CCP case series and review of the literature

OBJECTIVE: To describe the occurrence of erosive arthropathy in systemic lupus erythematosus (SLE) and its relationship to anti-CCP antibodies. METHODS: Retrospective medical record review of a case series of five female patients with SLE and erosive arthropathies. RESULTS: The initial disease presentation in all patients was a polyarthritis. Anti-CCP antibodies were detected in 4 out of 5 (80%) patients, 2 of whom had a positive rheumatoid factor. CONCLUSION: Erosive arthritis was strongly associated with the presence of anti-CCP antibodies in these patients with SLE, who presented with polyarthritis. Anti-CCP in patients with SLE may be a marker of a more severe joint disease.     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC Class II alleles in systemic lupus erythematosus

OBJECTIVE: To determine the associations of erosive arthritis (EA) with anti-cyclic citrullinated peptide (anti-CCP) antibodies and major histocompatibility class (MHC) II alleles in systemic lupus erythematosus (SLE). METHODS: One hundred four patients with SLE were evaluated for arthritis and classified as EA, nonerosive arthritis, or no arthritis. EA was further classified as major or minor erosions. Sera from patients and 130 serum controls were tested for anti-CCP2 and rheumatoid factor (RF). Patients and 117 genetic controls were genotyped for HLA-DRB1 and HLA-DQB1. Statistical associations were tested using chi-square tests and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Eight patients (8%) were anti-CCP+ and they accounted for 11% (8/71) of patients with synovitis. Twelve patients (11%) had EA. Among patients with synovitis, EA was associated with anti-CCP (OR 28.5, 95% CI 4.7-173.8, p = 0.001), with a weaker association for RF (p = 0.3). Six patients with EA had major erosions and also met criteria for rheumatoid arthritis (RA). Four of these patients (67%) were anti-CCP+. HLA-DQB1*0302 was associated with EA (p = 0.01), with similar trends for HLA-DRB1*0401 and 2 copies of the shared epitope (SE). There were trends for associations of HLA-DQB1*0302 and 2 SE copies with anti-CCP production. CONCLUSION: The frequency of EA in SLE is likely to be higher than previously reported. Anti-CCP+ patients with SLE are more likely to have EA. Anti-CCP may be a useful serological marker for EA for patients presenting with synovitis. Anti-citrulline antibodies may have a pathogenic role in the development of major erosions, resulting in clinical features that overlap SLE with RA (rhupus).     

Antibodies to cyclic citrullinated peptides in psoriatic arthritis

OBJECTIVE: To determine the presence and clinical significance of antibodies to cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA). METHODS: We performed a cross-sectional study on 102 outpatients (56 men) with PsA consecutively recruited from a tertiary referral center. Median disease duration was 36 months (interquartile range 21-81). All patients were investigated for peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and feet were performed in all cases. RESULTS: Anti-CCP were detected in 16/102 patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis, 2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with exclusive axial or distal interphalangeal (DIP) involvement. The male:female ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or DIP joint involvement were similar in the anti-CCP positive and negative groups. Anti-CCP positive patients were more frequently treated with disease modifying antirheumatic drugs and showed higher number of involved joints, and higher frequency of erosive arthritis and positive RF. Using multiple logistic regression, anti-CCP (but not RF) were significantly associated with erosive arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and > or = 10 involved joints (17.99; 3.6-89.2). CONCLUSION: Anti-CCP can be found in a small but significant proportion of patients with a clinical picture of PsA and are associated with erosive arthritis and multiple joint involvement.     

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.     

Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile rheumatoid arthritis (JRA), particularly in those with polyarticular, rheumatoid factor (RF)-positive JRA. Our objectives were to determine whether anti-CCP antibodies are associated with HLA-DR4 in children with polyarticular JRA, whether anti-CCP antibodies are associated with clinical features of disease, and whether affected sibling pairs (ASPs) with JRA are concordant for this antibody. METHODS: Stored serum samples obtained from 230 HLA-typed patients with JRA (77 with polyarticular-onset disease and 153 with pauciarticular- or systemic-onset disease), 100 JRA ASPs, and 688 healthy children were tested for anti-CCP antibodies and RF. RESULTS: Thirteen percent of the patients with polyarticular-onset JRA and 2% of the other JRA patients exhibited anti-CCP antibodies, compared with only 0.6% of the controls. Fifty-seven percent of RF-positive patients with polyarticular-onset JRA had anti-CCP antibodies. HLA-DR4-positive patients with polyarticular-onset JRA were more likely to have anti-CCP antibodies than were those without HLA-DR4 alleles (odds ratio [OR] 5.20, 95% confidence interval [95% CI] 1.30-20.9). Anti-CCP antibodies were associated with polyarticular onset (OR 7.46, 95% CI 1.99-28.0), a polyarticular disease course (OR 9.78, 95% CI 1.25-76.7), and erosive disease (OR 14.3, 95% CI 3.01-67.9). Concordance rates for anti-CCP antibodies among ASPs were statistically significant. CONCLUSION: These data demonstrate increased anti-CCP antibody formation in HLA-DR4-positive patients with polyarticular-onset JRA. The overall prevalence of anti-CCP antibodies in JRA is low, but a substantial proportion of RF-positive patients with polyarticular-onset JRA have these antibodies. Anti-CCP antibodies in JRA are associated with polyarticular onset, a polyarticular course, and erosive disease.