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1.
Sizova L 《Human immunology》2012,73(4):389-392
The aim of this study was to evaluate the usefulness of antibodies to modified citrullinated vimentin (anti-MCV) for diagnosing early rheumatoid arthritis (RA) and to examine the correlations between anti-MCV and clinical parameters as well as radiographic and ultrasound data. Our results suggest that anti-MCV has a sensitivity and specificity of 53.3 and 83.3%, respectively, and a positive prognostic value of 96% in patients with early RA. Anti-MCV antibodies were observed in 48.5% of rheumatoid factor (RF)-negative RA patients in data from a latex test and in 35.7% of patients with negative results for immunoglobulin (Ig)-M-RF. The positive result for both anti-MCV and IgM-RF has a sensitivity of 42.2% and a specificity of 100%. No significant correlation was observed between anti-MCV and disease activity score using 28 joint counts, radiographic RA stage, number of erosions on ultrasonography of joints, and quality-of-life scores at disease onset. The Spearman correlation was significant in early RA patients with positive results of anti-MCV between the titers of this marker and arthritis duration, level of erythrocyte sedimentation rate, and IgM-RF. The best diagnostic strategy in early RA may be to assay both anti-MCV and IgM-RF. Thus, a question arises regarding the possible inclusion of anti-MCV in future revisions of the classification criteria of RA.  相似文献   

2.
目的:评价抗突变型瓜氨酸波形蛋白(抗MCV)在类风湿关节炎(RA)诊断中的价值。方法:检测225例RA患者、77例其他关节炎患者以及80例正常对照血清中抗MCV、抗CCP和RF-IgM的水平,比较抗MCV、RF-IgM、抗CCP及抗MCV和抗CCP联合检测在类风湿关节炎的诊断中的意义。结果:①抗MCV、RF-IgM、抗CCP敏感性和特异性分别为74.67%、91.71%;77.78%、91.71%;65.33%、94.27%,抗MCV与抗CCP联合检测可明显提高诊断特异性,对RA诊断的敏感性和特异性分别为60.89%、99.36%;②抗MCV与抗CCP检测对RF阴性RA病例的诊断有一定价值(30%,26%);③抗MCV、抗CCP与RF-IgM之间均显著相关(P〈0.01);④抗MCV与年龄、病程、功能分级、压痛关节数、ESR、CRP、X线分期及晨僵持续时间存在相关(P〈0.01或P〈0.05),而与性别、双手平均握力和肿胀关节数无关(P〉0.05)。结论:抗MCV对RA有较高的诊断价值,抗CCP和抗MCV联合检测对RA有高度特异性,抗MCV能一定程度反映RA的临床病情,可作为RA的血清学指标。  相似文献   

3.
Anti-citrullinated protein/peptide antibodies (ACPA) are a hallmark of rheumatoid arthritis (RA) and can be measured using different citrullinated substrates. In this paper we describe a new viral citrullinated peptide - VCP2 - derived from the Epstein-Barr virus-encoded protein EBNA-2 and analyse its potential as substrate for ACPA detection. Analysing sera from 100 RA patients and 306 controls, anti-VCP2 immunoglobulin (Ig)G were found in 66% of RA sera, IgM in 46% and IgA in 39%, compared with less than 3% of control sera. Anti-VCP2 IgG was associated with erosive arthritis, the presence of rheumatoid factor and anti-VCP1 and anti-cyclic citrullinated peptide (CCP) antibodies. Anti-VCP2 antibodies were detected in 1% and anti-VCP1 antibodies in 4% of CCP-negative RA sera; conversely, 3% of the VCP-negative sera were CCP-positive. Taken together, these data suggest that VCP2 could offer a valuable tool for ACPA detection. Inhibition assays showed that two non-overlapping epitopes - a citrulline-glycine stretch shared between VCP1 and VCP2 and the N-terminal portion of the VCP2 sequence - were targeted by anti-VCP2 antibodies. Moreover, in some RA sera that tested positive in CCP and VCP2 assays, preincubation with VCP2 inhibited binding to CCP, whereas in other sera the binding was unaffected. Thus, the reactivity with more than one ACPA substrate might be due in some RA patients to antibody populations with different specificities, and in others to cross-reactive antibody populations. Finally, affinity-purified anti-VCP2 antibodies immunoprecipitated deiminated Epstein-Barr virus nuclear antigen (EBNA-2) from an EBNA-2-transfected cell line, suggesting that viral sequences may be involved in the generation of the ACPA response.  相似文献   

4.
Anti-citrullinated protein/peptide antibodies (ACPA) are the principal autoantibody system associated with rheumatoid arthritis (RA), with diagnostic sensitivity of 70% and specificity of 95%. Current testing for ACPA uses the anti-cyclic citrullinated peptide assay (anti-CCP) which measures a generalized reactivity with citrulline-containing peptides, thus giving no insight into reactivity to specific RA antigens. Of these, the best characterized are, α-enolase, fibrinogen/fibrin, vimentin, Type 2 collagen and filaggrin, antibodies to each of which are found in approximately 30–60% of RA cases. Given reports of cross-reactivity between citrullinated antigens, we discuss whether or not measuring these specific antibodies could aid: clinical diagnosis, identification of clinical subsets and drug responses, or provide insight into pathogenic mechanisms or etiology of RA.  相似文献   

5.
Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a new diagnostic marker for rheumatoid arthritis (RA), which shows a specificity of 97% and a sensitivity of 81% in the second generation assay. About 61% of RA patients express HLA-DRB1*0401. In a cohort of patients with RA we investigated whether the expression of anti-CCP correlates with the carriage of certain genes on the HLA-DRB1 locus. Our data reveal a highly significant association between anti-CCP and HLA-DR4, and a weaker but still significant association with HLA-DR1. HLA-DRB1*0401 is not a prerequisite for anti-CCP production, but if HLA-DRB1*0401 was present, 90% of our RA patients were anti-CCP positive.  相似文献   

6.
Rheumatoid factor (RF) has been commonly used as a marker of rheumatoid arthritis (RA). RF can be detected in 60-80% of RA patients, but the specificity is low against other rheumatic diseases patients. We evaluated the diagnostic accuracy of anti-cyclic citrullinated peptide antibody (anti-CCP), a new diagnostic test for RA. Anti-CCP demonstrated higher sensitivity (81.0%) and specificity (92.4%). By the receiver operating characteristic (ROC) curve analysis, anti-CCP was superior to other markers (ie. RF, CARF, IgG-RF, and MMP-3). In early RA patients (RA patients who had had disease symptoms for < 2 years), sensitivity was 68.8%. Positivities of anti-CCP in RA patients became higher as the advance of stage defined by the Steinbrocker classification. We concluded that anti-CCP is a very valuable tool for the diagnosis of RA. Moreover, anti-CCP is a useful for finding RA of recent onset.  相似文献   

7.
Anti-citrullinated protein antibodies (ACPAs) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. The first members of this autoantibody family were anti-perinuclear factor (APF) and anti-keratin antibodies (AKA). It became evident that both APF and AKA recognize citrullinated epitopes of filaggrin. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets for anti-filaggrin antibodies led to the development of the first and later second generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The widely used anti-CCP2 assays have high diagnostic sensitivity and specificity, and they also show important predictive and prognostic value in RA. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin, hence it is a new member of the family of ACPAs. The newly developed anti-mutated citrullinated vimentin (anti-MCV) assay has similar diagnostic performance than the anti-CCP2 ELISA; however, the diagnostic spectrum of the anti-MCV test is somewhat different from that of anti-CCP2. It’s especially useful in the diagnosis of RA in RF and anti-CCP2 seronegative patients. The combined application of anti-CCP2 and anti-MCV assays can improve the laboratory diagnostics of RA. The family of ACPAs is expected to expand; there is an increasing need for developing new diagnostic strategies after careful evaluation of the characteristics of the available assays. Zoltán Szekanecz and Lilla Soós with equal contribution.  相似文献   

8.
The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP (95.2%). dACRF positive predictive value was high (98.2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.  相似文献   

9.
Antibodies to citrullinated proteins/peptides (ACPAs) are the second serological marker to have recently been included in the 2010 ACR/EULAR Rheumatoid Arthritis (RA) Classification Criteria, which are focused on early diagnosis and therapy. This review discusses their history and some clinical aspects of ACPAs, focusing on the diagnostic utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies as a marker of RA as compared to the widely used rheumatoid factor (RF). Simultaneously, this review aims to raise physician awareness and interest in anti-citrullinated vimentin antibody (anti-Sa/anti-MCV), another member of the ACPA family, which appears to have a better predictive value as a marker of RA than anti-CCP or RF and correlates closely with disease activity and therapeutic response among patients with RA.  相似文献   

10.
Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. We studied the diagnostic performances of anti-cyclic citrullinated peptides antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA assays were performed in 324 RA patients, 251 control patients, and 286 healthy subjects. The optimal cut off values of each assay were determined at the maximal point of area under the curve by receiver-operator characteristics (ROC) curve. Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In conclusion, we consider that anti-CCP could be very useful serological assay for the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than RF and AFA at the optimal cut off values and could be performed by easy, convenient ELISA method.  相似文献   

11.
Autoantibodies to citrullinated proteins: ACPA   总被引:4,自引:0,他引:4  
Anti-perinuclear factor and anti-keratin antibodies have long been known to be specifically associated with rheumatoid arthritis (RA). They were first demonstrated to target various forms of (pro)filaggrin, a protein of stratified epithelia. Then, they were found to belong to a single family of autoantibodies targeting proteins that bear peptidic epitopes centered by a citrullyl residue: the anti-citrullinated protein autoantibodies (ACPA). The main targets of ACPA in the synovial tissue were demonstrated to be citrullinated forms of the a- and beta-chains of fibrin. A chronic conflict between locally produced ACPA and deposits of citrullinated fibrin is probably responsible for self-maintaining of RA synovial inflammation. Various tests for the detection of ACPA have been developed: recent ELISAs confirm their high diagnostic specificity and improve their diagnostic sensitivity. Since ACPA appear very early in the course of the disease, their detection is of major interest to identify RA among recent arthritides. Moreover, their prognostic value may lead to start early 'aggressive' treatments to prevent irreversible joint damage.  相似文献   

12.
The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.  相似文献   

13.
Anti-citrullinated protein/peptide antibodies (ACPAs) have recently been identified as sensitive and specific diagnostic and prognostic markers in rheumatoid arthritis (RA). In this study, we wished to assess the diagnostic performance of the third-generation anti-CCP3.1 assay, but with special focus on the rheumatoid factor (RF)-negative RA population. Anti-CCP as well as anti-MCV was tested in 119 RA patients and 118 control patients using second and third-generation assays. Using these optimal cut-off levels, the diagnostic sensitivity of anti-CCP2, CCP3, and CCP3.1 was 74.8, 78.8, and 83.0 %, respectively, while the specificity was 95.7, 96.6, and 98.3 %, respectively. The diagnostic performance of the CCP3.1 test was significantly better than that of CCP2 (p = 0.041). In addition, the CCP3.1 test performed significantly better than the MCV test as well (p = 0.0003). When the diagnostic performance of the CCP3.1, CCP2, and MCV tests was compared in the 35 RF-negative patients, the CCP3.1 test exerted significantly better performance than the MCV test (p = 0.006), and it also showed a tendency of better performance in comparison with the CCP2 test (p = 0.131). In conclusion, the CCP3.1 assay can significantly increase the sensitivity of ACPA testing in RF-negative RA, as well as in the total RA population.  相似文献   

14.
The detection of anti-cyclic citrullinated peptides (CCP) antibodies is a new marker for diagnosis of rheumatoid arthritis. We screened 100 patients suffering from rheumatic pathologies or from other affections where rheumatoid factor is frequently detected. The screening was assessed by a second generation ELISA (Immunoscan RA) in comparison with agglutination assay (Latex and Waaler-Rose) and specific ELISA (IgM, IgG and IgA). The sensitivity of the anti-CCP is good (>70%) with an excellent specificity (98%). In our study the predictive value of the Immunoscan RA reached 71% and more among patients with joints symptoms. Anti-CCP antibody test could serve as a better diagnosis marker than rheumatoid factor.  相似文献   

15.
RF、AKA和抗CCP抗体联检对类风湿关节炎诊断的临床价值   总被引:3,自引:0,他引:3  
目的:探讨类风湿因子(Rheum atoid factor,RF)、抗角质蛋白抗体(antikeratin antibody,AKA)及抗环瓜氨酸肽(anti-cyc lic c itru llinated peptide,CCP)抗体对类风湿关节炎(rheum atoid arthritis,RA)的临床意义和早期应用价值。方法:对40例类风湿关节炎患者、30例系统性红斑狼疮和30名正常健康体检者进行RF、AKA、抗CCP抗体检测,应用速率散射比浊法测定RF,间接免疫荧光法检测AKA,ELISA法测定抗CCP抗体。结果:40例RA患者血清中,RF灵敏度和特异性分别为70.0%、90.0%,AKA灵敏度和特异性分别为35.0%、96.7%,抗CCP抗体灵敏度和特异性分别为85.0%、93.3%,联检RF、AKA及抗CCP抗体灵敏度和特异性分别为97.07%、99.8%。结论:RF、AKA和抗CCP抗体可作为诊断RA比较特异的血清学指标,三项指标联检可在一定程度上弥补RF对RA的诊断不足,提高RA的阳性诊断率,且有助于疾病的预后判断。  相似文献   

16.
目的为寻找敏感性高、特异性强的诊断类风湿关节炎(RA)的实验指标,选择抗环瓜氨酸肽(CCP)抗体、葡萄糖6-磷酸异构酶(GPI)和类风湿因子(RF)并探讨对RA的诊断价值。方法抗CCP抗体和GPI试验采用酶联免疫吸附(ELISA)法,RF用胶乳凝集法,检测了125例RA患者(RA组)、56例其他风湿性疾病患者(对照组)和36例健康体检者(正常组)血清中上述3者的浓度。结果抗CCP抗体、GPI及RF,在RA组分别是:(83.6±45.9)RU/ml、(2.8±2.3)μg/ml和(320.4±208.6)IU/ml;在对照组分别是:(36.2±15.3)RU/ml、(0.19±0.06)μg/ml和(36.3±12.5)IU/ml;在正常组分别是:(19.2±8.6)RU/ml、(0.16±0.08)μg/ml和(19.2±6.5)IU/ml。在RA组中,3者的敏感度分别是64.8%、73.6%和69.6%,特异性分别是92.0%、72.8%和74.4%。结论 RA患者血清抗CCP抗体、GPI和RF显著高于其他疾病患者(P<0.01)。抗CCP抗体和GPI有可能成为诊断RA的新指标、RA的血清标志物,对提高诊断RA的敏感性和特异性,具有良好的临床研究和推广价值。  相似文献   

17.
目的探讨抗环瓜氨酸肽抗体(抗CCP抗体)检测对类风湿关节炎(RA)诊断的意义。方法采用酶联免疫吸附试验(ELISA)检测115份人血清的抗CCP抗体,同时采用免疫透射比浊法定量检测类风湿因子(RF),包括40例RA患者,45例其它风湿病患者,30名正常人;并分析抗CCP抗体与RF实验结果之间的相关性。结果在40例RA病人中,抗CCP抗体的阳性率为80.0%,在其它风湿病人中的阳性率为7.0%,抗CCP抗体对RA的敏感性和特异性分别为80.0%、96.0%,其敏感性高于RF,但差异无统计学意义(P〉0.05),特异性明显高于RF(P〈0.05)。联合应用抗CCP抗体与RF进行诊断,二者均阳性时敏感性为65.0%,特异性为97.3%。抗CCP抗体与RF实验结果之间无相关性。结论抗CCP抗体对RA具有较好的敏感性和很高的特异性,可与RF相互补充,联合检测可提高对RA早期诊断的准确性。  相似文献   

18.
Rheumatoid arthritis [RA] is one of the most common and severe autoimmune rheumatic diseases, diagnosed primarily according to clinical manifestations and radiological reports. For many years, laboratory diagnosis of rheumatoid arthritis has relied on the detection of rheumatoid factor [RF], as established by the ACR criteria. A recent test to detect antibodies towards citrullinated peptides, called the anti-CCP assay, showed a similar sensitivity but a more elevated specificity than the RF test. Our intention was the recognition of an optimal diagnostic strategy that exhibits the highest sensitivity and specificity for RA detection. To this purpose, we examine the usefulness of autoantibodies in RA testing, evaluating the diagnostic performance of conventional and innovative assays for RF detection, and ELISA anti-CCP test, for anti-CCP antibodies detection, by a prospective study. Multiplex cytofluorimetric test appeared to be more sensitive and specific than nephelometric assay for RF detection. Hence, a novel combined approach, significantly increasing the diagnostic sensitivity for RA, was planned, employing the multiplex RF test in combination with the anti-CCP test.  相似文献   

19.
Anti-CCP: history and its usefulness   总被引:3,自引:0,他引:3  
Antibodies directed to cyclic citrullinated peptides (anti-CCP) are highly specific for rheumatoid arthritis (RA) and can easily be detected in sera by using commercially available immunoassays. The second version of the anti-CCP test (anti-CCP2) demonstrated high specificity (89-98%) and good sensitivity (41-88%) for RA. Commercially available ELISA methods from three different companies are on the market. All three CCP2 assays show similar results as all CCP2 assays use the same antigen-coated plates. This study was an evaluation of a new automated method for the determination of anti-CCP2 in a routine laboratory setting. Five hundred and forty three serum samples were tested for anti-CCP2 within normal routine diagnostic using a commercially available ELISA and retested with a prelaunch version of a new and fully-automated method (EliA). The results were comparable. The new automated assay is easy to use and demonstrated a diagnostic sensitivity of 80% and specificity of 97%.  相似文献   

20.
OBJECTIVE: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). METHODS: We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. RESULTS: The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher frequency of elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. CONCLUSION: The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.  相似文献   

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