Diagnostic utility of anti-cyclic citrullinated peptide antibodies for rheumatoid arthritis in patients with active lung tuberculosis

This study was intended to evaluate the utility of anti-cyclic citrullinated peptide antibodies (second generation, anti-CCP2) as a diagnostic marker for rheumatoid arthritis (RA) in patients with active tuberculosis. Among 89 patients with active tuberculosis, anti-CCP2 was detected in six (6.7%), and three of these (3.4%) were strongly positive for anti-CCP2. The positive rate of anti-CCP2 in patients with newly diagnosed RA was 82.1% (87 of 106 cases), while the rate in healthy control subjects was 0.4% (one of 237 individuals). The mean level of anti-CCP2 among the RA group was 159.3 U/ml, which was significantly higher than both that among the tuberculosis group (15.4 U/ml) and that among the healthy controls (0.7 U/ml). IgM rheumatoid factor (RF) was detected in 16 patients from the tuberculosis group (18.0%) with a mean serum level of 18.6 IU/ml and in 77 patients of the RA group (72.6%) with a mean level of 164.0 IU/ml. Only two cases in the tuberculosis group were positive for both anti-CCP2 and IgM RF. These observations show that measurement of anti-CCP2 seems to be a reliable serological tool for identifying early RA in patients with active tuberculosis.     

Value of anti-mutated citrullinated vimentin antibodies in diagnosing rheumatoid arthritis

We assessed the diagnostic value of anti-mutated citrullinated vimentin antibodies (anti-MCV) and compared it with those of anti-cyclic citrullinated peptide antibodies (anti-CCP), IgA (ARF), IgM (MRF) and IgG (GRF) rheumatoid factors for rheumatoid arthritis (RA). Serum samples of 170 RA patients, with early and established RA, and 309 controls were tested for anti-MCV, anti-CCP, ARF, MRF and GRF using commercially available ELISA kits. Cut off of different tests was determined with ROC curves. The sensitivity and the specificity of anti-MCV were 74.1 and 79%, respectively. Sixty-five of 309 (21%) controls were anti-MCV positive. Sensitivity and specificity of anti-CCP were 72.4 and 96.1%, respectively. Only 12 of 309 (3.9%) controls were anti-CCP positive. Sensitivity of ARF, MRF and GRF were 64.1, 65.9 and 68.2%, respectively. Their specificity was 79.6, 74.4 and 68.9%, respectively. No significant association was observed between the antibodies tested and extrarticular manifestations. Anti-MCV shows comparable sensitivity but lower specificity than that of anti-CCP. They do not appear to be very useful in the diagnosis of RA.     

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。     

Serum IgG activity against cyclic citrullinated peptide in patients evaluated for rheumatoid factor correlates with the IgM isotype

The purpose of this study was to evaluate the frequency of seric antibodies against cyclic citrullinated peptide (a-CCP) in patients tested for rheumatoid factor (RF) reactivity, and to analyze the correlation between their titers. We obtained serum from 112 consecutive patients (85 female), aged 47.2 +/- 13.4 years and from 46 clinically healthy subjects (CHS). Patients where stratified into four subgroups: rheumatoid arthritis (RA), probable RA (PRA), spondylarthropathies and other diagnosis. The a-CCP antibodies were determined by enzyme linked immunoassay (ELISA), RF by nephelometric test (IgM) and ELISA (IgG and IgM). Analysis of variance (ANOVA) showed statistically that a-CCP antibodies differs among RA versus CHS and other diagnosis; PRA versus CHS and other diagnosis. A significant Rho value of 0.84 (P < 0.05, Spearman's correlation) was identified between a-CCP antibodies and RF in PRA subgroup. When a correlation of a-CCP antibodies with RF (both isotypes) was done, the higher correlation was observed against IgM RF. The data suggests different pathways and times for each antibody generation.     

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。     

中国汉族类风湿关节炎患者HLA-DR4基因与抗环瓜氨酸肽抗体的相关性研究

目的：探讨中国汉族类风湿关节炎（RA）患者中抗环瓜氨酸肽抗体（ACCP）与人类白细胞抗原（HLA）-DR4基因的相关性。方法：入选RA104例、正常对照122名。ACCP检测采用酶联免疫吸附法（ELISA）,类风湿因子检测采用散色比浊法,HLA-DR4基因采用序列特异性引物-聚合酶链方法（PCR-SSP）检测。结果：RA患者中HLA-DR4基因携带率为34.6%,主要亚型为HLA-DRB1＊0405,正常对照组为17.2%,差异有统计学意义（P=0.01）。RA患者的共同表位（SE）携带率为30.9%,与国内相关研究结果（33.2%,36.8%）相似,但明显低于国外相关研究（78.5%,65.4%,85%,67%）,差异有统计学意义（P〈0.01）。RA患者中ACCP阳性率为76.5%,与国内外报道相符,正常对照组为0,两者差异有统计学意义。SE（＋）患者的ACCP阳性率为84%,SE（-）患者的ACCP阳性率73.2%,两者差异无统计学意义。RA患者中ACCP的滴度与X线分期相关（r=0.233,P〈0.05）。结论：我国汉族RA患者中ACCP与HLA-DR4或SE无明显的相关性。ACCP可能与关节破坏的严重程度相关。     

抗环瓜氨酸肽抗体类风湿因子与类风湿关节炎活动度及骨侵蚀相关性的研究

目的探讨抗环瓜氨酸肽抗体（ACCP）及类风湿因子（RF）各亚型与类风湿关节炎（RA）疾病活动度及骨质侵蚀的相关性.方法收集110例RA患者,用SPSS10.0软件比较ACCP、RF（IgA、IgM、IgG）与病情活动指数（disease activity score,DAS）、Ritchie′s指数（Ritchie′s articular index,RAI）的相关性,以判断ACCP、RF（IgA、IgM、IgG）与疾病活动度的关系.将病程＞2年的病例分为骨质侵蚀组和非骨质侵蚀组,比较两组之间ACCP、RF（IgA、IgM、IgG）的差异.结果经Spearman相关分析,IgM-RF与RAI呈正相关,ACCP及RF其他亚型与DAS、RAI未显示明显相关性.ACCP、RF各亚型与骨质侵蚀均未表现明显相关性.结论IgM-RF与疾病活动度相关,ACCP及RF各亚型与骨质侵蚀未表现出相关性.     

Clinical utility of anti-carbamylated antibody in rheumatoid arthritis female patients: Emerging predictive value compared to anti-cyclic citrullinated peptide and rheumatoid factor

Aim of the workTo evaluate the frequency of anti-carbamylated protein (anti-CarP) antibodies positivity in female rheumatoid arthritis (RA) patients; to study their association with different disease aspects clinically and radiologically and to assess their potential predictive role of RA disease compared to other autoantibodies.Patients and methodsFifty-one RA female patients and 44 age-matched controls were studied. Duration of morning stiffness, disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Laboratory investigations included acute phase reactants, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies. Conventional radiography of both hands and feet was performed and assessed by a simple erosion narrowing score (SENS). All patients were evaluated by ultrasound 7 (US7) score.ResultsThe mean age of patients was 46.9 ± 8.6 years with disease duration of 6.2 ± 5.3 years. Anti-CarP antibody was positive in 52% and 54.5% of patients seronegative for anti-CCP and RF respectively. RF was positive in 40 (78.4), anti-CCP was positive in 26(51%), and anti-CarP in 21 (41.2%) patients. Anti-CarP antibodies were significantly associated with radiological damage, DAS28, HAQ and acute phase reactants. The sensitivity and specificity were 41.2% and 88.6%, respectively for anti-CarP, 51% and 93.2% for anti-CCP and 78.4% and 90.9% for RF to diagnose RA.ConclusionsAn association between anti-CarP antibody positivity and the disease activity, severity, structural damage and hence poor disease outcome has been demonstrated. Testing anti-CarP antibodies could be a useful marker for the assessment of disease activity as well as the expectation of prognosis in RA patients.     

抗突变型瓜氨酸化波形蛋白抗体检测在类风湿关节炎中的意义

目的 评价抗突变型瓜氨酸化波形蛋白（MCV）抗体在类风湿关节炎（RA）诊断中的价值。方法 检测136例RA患者，80例其他结缔组织病患者以及19名正常对照血清中抗MCV抗体的分布，比较抗MCV抗体与类风湿因子（RF）、抗环瓜氨酸肽（CCP）抗体和抗角蛋白抗体（AKA）的相关性，并分析上述抗体在RA诊断中的意义。结果 136例RA患者抗MCV抗体敏感性和特异性分别为95．6％和80．8％．与非RA对照组比较差异有统计学意义（P〈0．05）。抗MCV抗体与抗CCP抗体、AKA和RF的重叠阳性率分别为91．9％、52．8％和76．5％。经统计学分析，抗MCV抗体与抗CCP抗体、AKA和RF之间存在相关性。结论 抗MCV抗体对RA有较高的诊断价值，可视为RA新的血清学诊断指标．能提高RA的早期诊断率。     

用受试者工作曲线评价抗环瓜氨酸肽抗体对诊断类风湿关节炎的价值

目的评价抗环瓜氨酸肽抗体(抗CCP抗体)在类风湿关节炎(RA)诊断中的价值。方法收集110例RA患者,与38例其他疾病患者以及36名正常人作为对照,应用受试者工作曲线(re-ceiveroperativecharacteristiccurve,ROC)分析软件评价抗CCP抗体在RA诊断中的价值,在ROC曲线上制定抗CCP抗体与类风湿因子(RF)各亚型在诊断RA中的最佳临界点。用四格表计算系列试验的特异度,进行统计学检验。用SPSS软件比较抗CCP抗体与RF各亚型之间的相关性。结果在诊断RA中,抗CCP抗体的ROC曲线下的面积(AUCROC)明显大于RF(IgA、IgM、IgG)AUCROC(P<0.01),抗CCP抗体联合任何一个RF亚型的系列试验的特异度高达100%。抗CCP抗体和RF(IgA、IgM、IgG)经Spearman相关分析,呈正相关。结论抗CCP抗体对RA有较高的诊断价值;诊断RA的系列试验中,含抗CCP抗体的系列试验的特异度高。     

Diagnostic performances of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis

To evaluate the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic citrullinated peptide antibodies (anti-CCP). Anti-CCP was detected by an enzyme linked immunosorbent assay in 164 patients with RA and 343 controls. In addition, anti-CCP predictive value for radiological damage were investigated in 37 recent-onset RA patients followed up prospectively for 2 years. Radiological damages were assessed by Sharp method modified by van der Heijde. The sensitivity of anti-CCP was 78.7% and the specificity was 95.6%. The positive predictive value and the negative predictive value were 90.2% and 90.3%, respectively. Anti-CCP were detected in sera of 79.3% of patients with recent onset RA and 78.3% of patients with long disease duration. In univariate and multivariate analyses, anti-CCP were not predictive for radiological damage. Our study confirms the high diagnostic performances of anti-CCP in RA. They are very useful to aid the diagnostic of RA in clinical practice.     

Anti-cyclic citrullinated peptide-2 (CCP2) autoantibodies and extra-articular manifestations in Greek patients with rheumatoid arthritis

The objective of our study was to establish whether there is an association between rheumatoid arthritis with extra-articular manifestations (exRA) and anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies in Greeks. A retrospective study of 220 Greek patients with RA, 95 with exRA and 125 without extra-articular manifestations (cRA). Serum anti-CCP2 antibodies and IgM rheumatoid factor (RF) were measured. CCP2(+) were 65.3% of exRA and 58.4% of cRA patients. RF(+) were 69.5% of exRA and 60.0% of cRA patients. Among exRA patients, 37.9% had high serum anti-CCP2 antibody levels (>100 IU/ml) compared to 21.6% cRA patients (p = 0.008). Serositis and pulmonary fibrosis were found to be associated with high levels of anti-CCP2 antibodies (52.9 vs 26.6%, p = 0.02 and 63.6 vs 26.8%, p = 0.008, respectively). Serum RF levels were 265.0 ± 52.0 IU/ml (mean ± SEM) in exRA and 205.1 ± 40.6 (mean ± SEM) in cRA (NS). High serum RF levels (>268 IU/ml) were more likely to have sicca syndrome. In Greek patients with rheumatoid arthritis (RA), high serum anti-CCP2 antibodies are associated with serositis and pulmonary fibrosis. Therefore, anti-CCP2 antibodies have prognostic significance in patients with RA.     

Incidence rate of falls and its risk factors in patients with rheumatoid arthritis compared to controls: Four years of the TOMORROW study

Objective: Patients with rheumatoid arthritis (RA) have been recognized to experience falls frequently due to functional disabilities. The aim of this study was to prospectively investigate factors influencing falls in patients with RA compared to controls.

Methods: We compared the frequency of falls in 208 RA patients and 205 age- and sex-matched volunteers for four years and analyzed risk factors for falls in RA patients using multivariate regression analysis.

Results: No significant difference in the incidence rate of falls (/person-year) between patients with RA (median [interquartile range]: 0 [0, 0.5]) and controls (0 [0, 0.5]) was evident during four years. Logistic regression analysis identified age, sex, body mass index, history of falls, and lower limb implant at baseline as significant risk factors for falls. The highest quartile of anti-CCP antibody level (>300.6?U/ml) was the strongest predictor for multiple falls (odds ratio, 2.97; 95% confidence interval, 1.12–7.91, p?=?0.029) among RA patients.

Conclusion: During four years we could not observe the higher incidence rate of falls in RA patients compared to controls in our cohort. Subjects with a higher titer of anti-CCP antibody might be at higher risk of frequent falls among RA patients.     

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。     

Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RA

The purpose of this study was to identify rheumatoid arthritis (RA)-related autoantibodies in subjects with interstitial lung disease (ILD) and no articular findings of RA, supporting the hypothesis that RA-related autoimmunity may be generated in non-articular sites, such as the lung. This was a retrospective chart review utilizing clinic databases of patients with ILD to identify cases with lung disease, RA-related autoantibody positivity, and no clinical evidence of articular RA. Four patients with ILD, RF, and anti-CCP positivity and no articular findings of RA were identified. All four patients were male with a mean age at time of diagnosis of ILD of 70 years old. All had a history of smoking. Three patients died within 2 years of diagnosis of ILD and never developed articular symptoms consistent with RA; the final case met full criteria for articular RA several months after stopping immunosuppressive treatment for ILD. RF and anti-CCP can be present in smokers with ILD without clinical evidence of articular RA and in one case symptomatic ILD and autoantibody positivity preceded the development of articular RA. These findings suggest that RA-specific autoimmunity may be generated due to immunologic interactions in the lung and may be related to environmental factors such as smoking.     

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).     

Ethnic differences in the prognostic utility of rheumatoid factor isotypes and anticyclic citrullinated peptides in rheumatoid arthritis patients: a cross-sectional study

Abstract

Objectives The prognostic significance of rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) in rheumatoid arthritis (RA) remains contentious due to the conflicting lines of evidence. This study aims to determine the association between RF isotypes and anti-CCP with disease severity in RA patients from three ethnic groups.

Methods A total of 147 RA patients from three different ethnic groups (Malays, Chinese, and Indians) who fulfilled the 1987 American College of Rheumatology (ACR) revised criteria for RA were recruited into this study. The seroprevalence of RF isotypes immunoglobulin (Ig)A, IgG, and IgM, as well as anti-CCP was determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Multinomial regression analysis was performed to assess the independent effects of autoantibody status on the development of deforming and erosive RA and the presence of extra-articular manifestations (EAM).

Results In Chinese patients, we found a significant association (p < 0.05) between IgG RF and anti-CCP and the presence of erosive disease, as well as IgM RF and IgG RF with the presence of joint deformities. In Indian patients, IgM RF was associated with deforming disease, whereas none of the antibodies were associated with disease severity in Malay patients. Multinomial regression analysis revealed that IgG RF was the most important predictor variable for erosive disease in Chinese patients, and IgM RF the only predictor variable associated with deforming disease in both Chinese and Indian RA patients.

Conclusions There is variability in the phenotypic association of RF isotypes and anti-CCP in relation to disease severity of RA in the three ethnic groups. RF, in particular, IgG and IgM, may be better prognosticators of severe disease in Chinese and Indian patients.     

抗瓜氨酸肽抗体谱在幼年类风湿关节炎诊断中的意义

目的探讨抗环瓜氨酸肽抗体（抗CCP抗体）、类风湿因子（RF）、抗核周因子（APF）、抗角蛋白抗体（AKA）对幼年类风湿关节炎（JRA）诊断的意义，并与类风湿关节炎（RA）进行比较。方法分别采用酶联免疫吸附试验（ELISA）、胶乳凝集法、间接免疫荧光法检测54例JRA患者、31例非RA对照组、116例成人RA患者血清中的抗CCP抗体、RF、APF、AKA。结果54例JRA患者抗CCP抗体、RF、APF、AKA的敏感性分别为61．1％、57．4％、37．0％、18．5％，特异性分别为96．8％、93．6％、96．8％、100％。抗CCP抗体与RF在JRA的敏感性差异无统计学意义，但明显高于APF、AKA;4种抗体在JRA的特异性比较差异无统计学意义。RA患者中4种抗体敏感性分别为82．3％、78．3％、48．7％、25．4％，特异性分别为95．7％、7．3．7％、91．6％、94．0％。4种抗体在JRA诊断中的敏感性均明显低于RA组，RF在JRA患者中特异性明显高于RA患者，而其他3种抗体的特异性在两组患者比较差异无统计学意义。结论虽然抗CCP抗体谱在JRA诊断中的敏感性不及RA组，但对JRA的诊断仍具有较好的敏感性和特异性，可用于JRA的诊断。     

抗环瓜氨酸肽抗体检测在类风湿关节炎中的诊断及预后意义探讨

目的 评价抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在鉴别类风湿关节炎(RA)和其他风湿性疾病中的意义．探讨RA骨侵蚀与上述两种抗体之间的相关性。方法采用横断面研究，在125例RA．56例其他风湿性疾病，55例非风湿性疾病中检测上述两种抗体，其中抗CCP抗体采用酶联免疫吸附试验(ELISA)法．IgM-RF采用速率比浊法。分析RA骨侵蚀与上述两种抗体之间的相关性。结果IgM-RF诊断RA的敏感性较抗CCP抗体高(RF58．4％，抗CCP抗体54．4％)(P=0．57)；但抗CCP抗体有更高的诊断特异性(抗CCP抗体94．6％，IgM-RF84．7％)(P=0．015)，且两种检测方法之间无相关性。联合检测抗CCP抗体和IgM-RF有很高的特异性98．2％．较单独检测IgM-RF有更高的阳性预测值(PPV)95．7％(P=0.019)．阴性预测值(NPV)有下降57.7％(P=-0.213)。抗CCP抗体阳性、IgM-RF阳性与RA骨侵蚀相关。结论抗CCP抗体与IgM-RF比较对RA有良好的诊断敏感性与特异性．可视为RA新的血清学诊断指标。抗CCP抗体与RA骨侵蚀的关系值得进一步研究。