Anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis

We analysed the presence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin (AKA) antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups with more than one year duration of the disease. Enzyme-linked immunosorbent assay (Immunoscan RA, Eurodiagnostica, The Netherlands) and an indirect immunofluorescence (IIF) test on rat oesophagus substrate (ImmuGloTM, Immco Diagnostics, Buffalo, USA) were used for the detection and quantification of anti-CCP and AKA antibodies in 140 patients with JIA (64 male and 76 female) aged 2-47 years (median 16.5 years). Overall, anti-CCP were found in 7/140 (5.0%) patients including 3/52 RF negative polyarthritis, 2/18 RF positive polyarthritis, 1/15 enthesitis related arthritis and 1/5 unclassifiable arthritis. AKA were detected in 40/140 patients (28.6%, p = 0.04) including 2/11 systemic arthritis, 2/32 oligoarthritis, 18/52 patients with RF negative polyarthritis (34.6%, p = 0.01), 14/18 RF positive polyarthritis (77.8%, p = 0.000002), 2/15 enthesitis related arthritis and 2/3 psoriatic arthritis. While simultaneous negativity for AKA and anti-CCP occurred in most (97/140; 69.3%) studied cases, simultaneous antibody positivity was found only in few (4/140; 2.9%) studied samples. We conclude that while AKA measured using IIF on rat esophagus can be detected approximately in one third of patients with definite JIA with more than 1 year duration of the disease, only rare occurrence of anti-CCP was observed. We conclude that AKA seem to be partly useful to confirm JIA diagnosis, however, useless to follow-up severity or activity in JIA patients. Anti-CCP do not have any additional value in MA cohort in comparison to RA where their diagnostic and prognostic importance was reported.     

Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis: As Good as it Gets?

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.     

类风湿关节炎四种自身抗体的检测及意义

为评估类风湿因子(rheumatoid factor,RF)、抗环瓜氨酸肽(cyclic citrullinated pepdide,CCP)抗体、抗Sa抗体和抗角蛋白抗体(anti-keratin antibody,AKA)自身抗体对类风湿关节炎(rheumatoid arthritis,RA)诊断的意义,采用速率散...     

类风湿因子及相关自身抗体对类风湿关节炎的诊断价值

目的探讨类风湿因子（RF）、抗环瓜氨酸肽抗体（抗CCP）及抗角蛋白抗体（AKA）联合检测对类风湿关节炎（RA）的临床诊断价值。方法对80例RA和65例非RA的其他自身免疫病患者检测RF、RF-IgM、抗CCP及AKA 4种指标。结果自身免疫性疾病女性发病较高,以RA组为甚;RA组的RF、RF-IgM、抗CCP及AKA高于其他自身免疫性疾病组;单指标检测RA诊断的敏感性为RF〉RF-IgM〉AKA〉抗CCP,特异性为RF-IgM〉抗CCP〉RF〉AKA。阳性预测值为抗CCP〉RF〉RF-IgM、AKA,阴性预测值为RF〉RF-IgM〉AKA〉抗CCP;以并联或串联方式联合检测均以RF、RF-IgM及抗CCP三联及RF、RF-IgM、抗CCP及AKA四联检测为佳,并联检测的敏感性分别为93%及97%,串联检测的特异性分别为98%及99%。结论 RF、RF-IgM、抗CCP及AKA 4种指标联合检测可提高对RA诊断的敏感性和特异性,对RA的早期诊断有较高价值。     

抗突变型瓜氨酸波形蛋白检测在类风湿关节炎中的意义

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。     

Comparison and relevance of rheumatoid factors, antikeratin antibodies and anti-cyclic citrullinated peptides antibodies in rheumatoid arthritis

OBJECTIVES: to evaluate specificity and sensibility of the rheumatoid factors (RF), the anti-cyclic citrullinated peptide antibodies (CCP) and the anti-keratin antibodies (AKA) according to the rheumatoid arthritis (RA) diagnosis; pathology other than RA with at least one of these marker positive; the significance of the flocculent fluorescence of the antibodies AKA by indirect immunofluorescence (IIF). METHOD: two hundred forty height patients were studied: 121 RA, 89 inflammatory rheumatisms, 23 non inflammatory rheumatisms, and 15 non rheumatic affections. The RF was investigated by nephelometry, the anti-CCP by immunofluorometry and the AKA by IIF on rat oesophagus. RESULTS: specificity and sensibility were respectively in a retrospective manner: 68% and 83% for the RF, 95% and 76% for the anti- CCP, 83% and 40% for the AKA during RA with evolution of less than one year. The rates of agreements were: RF versus CCP: 81%, RF versus AKA: 57%, CCP versus AKA: 73%. Twelve patients with pathologies different from RA have positive anti-CCP or AKA. Thirty three of the patients with anti-CCP level superior to 130 U/mL have flocculent AKA versus only 5% when the anti-CCP are lower than 130 U/mL. CONCLUSION: the RF and the anti-CCP are complementary in RA. Autoimmune and neoplasic pathologies are sometimes responsible for the positivity of the anti-CCP and the AKA. The flocculent aspect of AKA in IIF may be associated with raised concentrations of anti-CCP.     

Anti-cyclic Citrullinated Peptide Antibodies in Patients with Juvenile Idiopathic Arthritis

We analysed the presence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin (AKA) antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups with more than one year duration of the disease. Enzyme-linked immunosorbent assay (Immunoscan RA, Eurodiagnostica, The Netherlands) and an indirect immunofluorescence (IIF) test on rat oesophagus substrate (ImmuGloTM, Immco Diagnostics, Buffalo, USA) were used for the detection and quantification of anti-CCP and AKA antibodies in 140 patients with JIA (64 male and 76 female) aged 2-47 years (median 16.5 years). Overall, anti-CCP were found in 7/140 (5.0%) patients including 3/52 RF negative polyarthritis, 2/18 RF positive polyarthritis, 1/15 enthesitis related arthritis and 1/5 unclassifiable arthritis. AKA were detected in 40/140 patients (28.6%, p =0.04) including 2/11 systemic arthritis, 2/32 oligoarthritis, 18/52 patients with RF negative polyarthritis (34.6%, p =0.01), 14/18 RF positive polyarthritis (77.8%, p =0.000002), 2/15 enthesitis related arthritis and 2/3 psoriatic arthritis. While simultaneous negativity for AKA and anti-CCP occurred in most (97/140; 69.3%) studied cases, simultaneous antibody positivity was found only in few (4/140; 2.9%) studied samples. We conclude that while AKA measured using IIF on rat esophagus can be detected approximately in one third of patients with definite JIA with more than 1 year duration of the disease, only rare occurrence of anti-CCP was observed. We conclude that AKA seem to be partly useful to confirm JIA diagnosis, however, useless to follow-up severity or activity in JIA patients. Anti-CCP do not have any additional value in JIA cohort in comparison to RA where their diagnostic and prognostic importance was reported.     

RF、AKA和抗CCP抗体联检对类风湿关节炎诊断的临床价值

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。     

Diagnostic performances of anti-cyclic citrullinated peptides antibody and antifilaggrin antibody in Korean patients with rheumatoid arthritis

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.     

Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: An Italian multicentric study and review of the literature

In the last years, the detection of antibodies (Abs) against citrullinated peptides (ACPA) has largely replaced rheumatoid factor (RF) as the most helpful biomarker in the diagnosis of rheumatoid arthritis (RA). Current assays detect ACPA reactivity with epitopes on various different citrullinated proteins. Among these, anti-cyclic citrullinated peptide (CCP) Abs have been widely demonstrated to be an important diagnostic and prognostic tool because of their high specificity. Recently, citrullinated vimentin, a protein highly released in synovial microenvironment, has been identified as potential autoantigen in the pathophysiology of RA and an enzyme-linked immunosorbent assay (ELISA) for the detection of Abs directed against a mutated citrullinated vimentin (anti-MCV) was developed. Several recent studies evaluating the characteristics of anti-MCV in comparison to anti-CCP Abs, have given conflicting results. Anti-MCV have been demonstrated to perform better than anti-CCP as predictor of radiographic damage. Conversely, its additional diagnostic and prognostic role in comparison to anti-CCP in both early and established RA is controversial. Aim of this study was to evaluate the diagnostic performance of anti-MCV in RA and to compare it to anti-CCP and the recently developed assay targeting viral citrullinated peptide 2 (VCP2) in a large cohort of RA patients (n=285), healthy subjects and other disease controls (n=227). Anti-MCV resulted to have a sensitivity of 59% and a specificity of 92%. In comparison, anti-CCP and anti-VCP2 displayed a sensitivity of 77% and 61% and a specificity of 96% and 95%, respectively. Of interest, at the manufacturer recommended cutoff value of 20U/mL, a high percentage of healthy subjects as well as Epstein Barr (EBV) and hepatitis C (HCV) virus infected patients resulted anti-MCV positive. In our large cohort of RA patients, anti-MCV demonstrated lower sensitivity than anti-CCP and VCP2 test, thus not allowing to confirm previously published data. Moreover, the high rate of detection in infectious diseases limits its diagnostic value in undifferentiated arthritis.     

第二代抗环瓜氨酸肽抗体的检测在类风湿关节炎诊断中的意义

目的探讨抗环瓜氮酸肽（CCP）抗体的检测在类风湿关节炎（RA）诊断中的价值。方法ELISA法分别检测108例RA、89例非RA（其它风湿病患者）和78例健康体检者的抗CCP抗体；用间接免疫荧光法和速率散射比浊法检测抗角蛋白抗体（AKA）和类风湿因子（RF），分析CCP抗体的水平及与AKA、RF的相关性。结果抗CCP抗体的阳性率在RA中为87．4％（94／108），在非RA中为8．99％（8／89），正常人为0％（0／78）。3种抗体对RA诊断的敏感性和特异性分别为CCP87．4％、91．01％，AKA58．33％，82．24％，RF81．36％、75．35％。CCP抗体与AKA在RA患者血清中的阳性率之间差异非常显著，与RF差异不显著。3种方法的检测结果间存在相关性。结论用ELISA法检测血清中CCP抗体简便、结果可靠，对RA诊断具有高度的敏感性和特异性。     

抗CCP抗体和AKA在类风湿关节炎诊断的应用价值

目的 比较抗环瓜氨酸肽抗体(抗CCP抗体)和抗角蛋白抗体(AKA)在类风湿关节炎诊断中作用,探讨RA的早期诊断方法.方法 对已确诊的85例RA患者、74例非RA的自身免疫病患者同时测定抗CCP抗体(ELISA法)、AKA(间接免疫荧光检测).结果 抗CCP抗体对诊断RA的灵敏度和特异性分别为75.3％和93.2％;AKA对RA诊断的灵敏度和特异性分别为89.4％和85.14％.抗CCP抗体的灵敏度与AKA灵敏度差异无统计学意义(P＞0.05),特异性差异有统计学意义(P＜0.05);抗CCP抗体或AKA与二者联合检测的灵敏度差异有统计学意义(P＜0.05),特异性差异有统计学意义(P＜0.05).阳性预测值抗CCP抗体较高,阴性预测值以二者联合检测较好,Youden index二者联合检测比单独检测抗CCP抗体或AKA高.抗CCP抗体和AKA在检测RA组中抗CCP抗体和AKA同时阳性检出58例;抗CCP抗体或AKA阳性共检出85例.抗CCP抗体或AKA阳性率(96.5％)比二者同时阳性率(68.2％)大大提高.结论 抗CCP抗体、AKA对RA具有较好的灵敏度和高度的特异性,联合检测抗CCP抗体和AKA可作为早期RA患者及RF阴性RA患者的早期诊断指标.     

Diagnostic value and clinical significance of anti-CCP in patients with advanced rheumatoid arthritis

OBJECTIVES: To investigate the prevalence of anticyclic citrullinated peptide (anti-CCP) in patients with advanced rheumatoid arthritis (RA) and to compare it with those in control subjects. Further, to study the relation between the anti-CCP and the disease activity parameters in these patients. PATIENTS AND METHODS: Seventy-six RA patients who had a mean disease duration of 9.8 years were included. Eighty-three age-matched non-RA volunteers were enrolled as the control group. Disease duration, duration of morning stiffness, swollen and tender joint counts, hand deformity, patient's assessment of pain, anti-CCP, rheumatoid factor (RF) and acute phase proteins were evaluated. The functional disability was also assessed with the Modified Health Assessment Questionnaire (HAQ). RESULTS: Thirty-seven sera (48.7%) in the patient group and one serum (1.2%) in the control group were positive for anti-CCP. RF was positive in 45% of the RA cases and in 5% of controls. Sensitivity and specificity of anti-CCP reactivity for RA were 49.0% and 99.0%, respectively. HAQ score and duration of morning stiffness were found to be significantly associated with anti-CCP positivity. Disease duration, swollen joint count and anti-CCP positivity were the most important variables predicting hand deformity. CONCLUSION: The prevalence, sensitivity and specificity of anti-CCP in patients with advanced RA were found to be similar to those reported in patients with early disease. Anti-CCP was significantly associated with some parameters of both disease activity and severity. Anti-CCP might be a useful parameter in clinical evaluation of patients with advanced RA.     

Usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP) for the diagnosis of rheumatoid arthritis

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.     

Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins

Formation of the epitopes recognized by the rheumatoid arthritis (RA)-specific autoantibodies to citrullinated proteins (ACPA) on filaggrin and on the alpha- and beta-chains of fibrin, their synovial target, requires conversion of their arginyl residues into citrullyl residues, but is also affected by their amino-acyl environment. Using competition with five citrullinated filaggrin-derived peptides bearing major ACPA epitopes, we confirmed the close cross-reactivity between filaggrin and citrullinated fibrin. To identify the sequential epitopes recognized on fibrin by ACPA, 71 citrullinated 15-mer peptides derived from all the sites of the alpha- and beta-chains of fibrin harboring arginyl residues were tested by ELISA using ACPA-positive RA sera exhibiting different reactivity profiles to the five filaggrin peptides. We identified 18 fibrin-derived peptides bearing ACPA epitopes. Regarding the ability of fibrinogen arginyl residues to be citrullinated in vitro, 11 of the peptides likely correspond to in vivo targeted epitopes. Two out of them bear major epitopes and are located in the central globular domain of the protein. In the synovial tissue, fibrin citrullination and ACPA binding could impair fibrin degradation by plasmin. The immunological conflict between ACPA and fibrin could therefore sustain synovial inflammation not only via pro-inflammatory effector mechanisms but also via impairment of fibrinolysis.     

Fine specificity of anti‐citrullinated peptide antibodies discloses a heterogeneous antibody population in rheumatoid arthritis

Anti‐citrullinated peptide antibodies (ACPA) are highly specific for rheumatoid arthritis (RA). However, the predominant B cell epitopes have not yet been defined. The aim of this study was to examine the reactivity of ACPA against different peptides derived from citrullinated proteins and to investigate whether or not these antibodies constitute a homogeneous population. For this purpose, sera from patients with RA (n = 141), systemic lupus erythematosus (SLE) (n = 60), Sjögren's syndrome (SS) (n = 54) and healthy controls (n = 100) were tested for their reactivity against six citrullinated peptides derived from peptidyl arginine deiminase (PAD), vimentin (vim), alpha‐enolase (enol), fibrin, type II collagen (col‐II) and filaggrin, respectively. A non‐citrullinated control peptide derived from PAD was used as control (ctrlPAD^621–40). Antibody reactivity against each individual peptide was evaluated by enzyme‐linked immunosorbent assay (ELISA). Specificity and cross‐reactivity of ACPA were tested by using two prototype sera with homologous and cross‐inhibition assays. Specificity of ACPA from two prototype sera was confirmed by purification of anti‐peptide antibodies and homologous‐inhibition experiments. We found that sera from patients with RA reacted diversely with the six citrullinated peptides. More specifically, PAD^211–30 displayed 29·08% sensitivity, vim^60–75 29·08%, enol^5–21 37·59%, fibrin^617–31 31·21%, col‐II^358–75 29·97% and filaggrin^306–24 28·37%, while control ctrlPAD^621–40 showed no reactivity. All reactive peptides were found to be highly specific for RA. A notable cross‐reaction (>70%) was found mainly between filaggrin and the majority of anti‐citrullinated peptide antibodies. We concluded that ACPA in RA constitute a heterogeneous population with limited cross‐reactivity and without a predominant epitope.     

The case for measuring antibodies to specific citrullinated antigens

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.     

抗环瓜氨酸肽抗体检测对类风湿关节炎的临床诊断价值

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。     

Anti-cyclic citrullinated peptide antibodies are highly associated with severe bone lesions in rheumatoid arthritis anti-CCP and bone damage in RA

In the present study we investigated the predictive value of anti-cyclic citrullinated peptide antibodies (anti-CCP) in early rheumatoid arthritis (RA) with respect to the bone damage. Fifty-four patients with early RA (onset <12 months), 35 classified as established RA (onset >12 months), 33 healthy donors and 76 non-RA autoimmune diseases, were enrolled. Anti-CCP and IgG, IgA, IgM rheumatoid factors (RFs) were determined at baseline. Disease activity score (DAS 28) was calculated at the entry. Bone involvement was evaluated by X-rays and sonography. The specificity of anti-CCP was 98.4%; significantly higher than those of the IgM- (86.0%), IgA- (86.0%) and IgG-RFs (66.2%), respectively. Anti-CCP were detected in 23/54 (42.6%) early RA patients and in 16/35 (45.7%) established RA patients. In the early RA group, 6/33 (18.2%) of the patients without bone lesions, 12/16 (75%) with juxta-articular osteoporosis (JO) and 5/5 with joint erosions (JE) resulted positive showing a significant difference between the groups without and with radiological damage. In the established RA group a significant difference being between the group without radiological damage and that with JE was found. Finally, in patients without radiological lesions, examined by ultrasound, anti-CCP antibodies were detected only in subjects with pathologic findings (31.25%). Data here reported confirm that the presence of anti-CCP are specific for diagnosis of RA, of recent onset also and they are potentially useful as prognostic index of bone involvement.     

Prevalence of Autoantibodies to Cyclic Citrullinated Peptide in Patients with Rheumatic Diseases other than Rheumatoid Arthritis: A French Multicenter Study

Our objective was to evaluate the prevalence of autoantibodies to cyclic citrullinated peptides (anti-CCP aAbs) in a cohort of patients with a variety of inflammatory or non-inflammatory rheumatic diseases other than rheumatoid arthritis (RA). Six hundred and nine serum samples were tested for anti-CCP aAbs and for rheumatoid factor (RF) using enzyme-linked immunosorbent assays and immunonephelometry. The prevalence of anti-CCP aAbs and RF reached 10% and 25%, respectively, using the positive cutoff value suggested by the manufacturers. Using a higher cutoff value (50 U/ml) for both aAbs, the prevalence was lower with 6% and 16%, respectively. The specificity of both markers for RA thus reached 94% and 84%, respectively. Anti-CCP aAbs were found to be elevated in inflammatory and also in non-inflammatory rheumatic diseases in the same proportion. Clinical data obtained for 36 positive patients showed that 17% developed RA within 5 years. In conclusion, anti-CCP aAbs are clearly more specific than RF for RA. Follow-up of anti-CCP aAbs-positive patients with inflammatory or non-inflammatory rheumatic diseases other than RA could be important considering the predictive value of these aAbs for the development of RA.