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.     

抗突变型瓜氨酸波形蛋白抗体在类风湿关节炎中的诊断价值

目的 通过与类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体的比较,探讨抗突变型瓜氨酸波形蛋白(MCV)抗体对类风湿关节炎(RA)的诊断价值,方法采用酶联免疫吸附试验(ELISA)定量检测177例RA患者、46例其他风湿性疾病患者及48名健康对照者血清中抗MCV水平,并同时测定血清中抗CCP抗体、RF水平.采用t检验和χ2检验.结果 抗MCV抗体在RA组、疾病对照组及健康对照组的抗体平均滴度依次为(523±376)、(96±55)、(34±18)U/ml;此外,通过ROC曲线计算曲线下面积来确定最佳阳性阈值(分别以20、40、60、80、100、120、140 U/ml),结果为0.521、0.706、0.769、0.791、0.816、0.826、0.822.其中以抗MCV抗体≥120 U/ml为阳性阈值临床诊断效能最大.所以本研究以抗MCV抗体≥120U/ml为阳性阈值,对RA诊断的敏感性为78.0%,特异性为87.2%,阳件预测值及阴性预测值分别为92.0%和67.8%;抗MCV抗体对RA诊断的特异性与抗CCP抗体相当,但敏感性高于抗CCP抗体;与RF相比较,抗MCV抗体的敏感性和特异性均高于前者.抗MCV抗体联合抗CCP抗体或RF或三者联合检测对诊断RA的特异性提高到95.7%;此外,67例抗CCP抗体阴性的RA患者中有32例抗MCV抗体阳性,占55.2%,59例RF阴性的RA患者中有31例抗MCV抗体阳性,占52.5%.结论 抗MCV抗体可以作为RA的临床诊断血清学指标之一,与抗CCP抗体、RF联合柃测可提高对RA诊断的特异性.     

Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA

Introduction: Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity. Materials and methods: A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at −70°C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean±2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive. Results: The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05). Conclusion: Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.     

Is rheumatoid factor still a superior test for the diagnosis of rheumatoid arthritis?

The diagnosis of rheumatoid arthritis (RA) is based primarily on the 1987 revised American College of Rheumatology criteria for RA, which considers mainly the clinical symptoms. But typical clinical symptoms of RA are not manifested completely in early disease course. On the other hand, appreciable advantages have been made in the therapeutic strategy of RA in the last decade and highly effective disease-modifying anti-rheumatic drugs are available now for the control of RA. The treatment strategy for the control of early RA is aggressive. Thus, a highly specific and early diagnostic marker is needed for the detection of RA. Our study is an attempt to see the role of anti-CCP2 antibody (claimed to be highly specific and early diagnostic tool) in the diagnosis of RA. We studied 119 cases of RA in terms of clinical symptoms, disease duration and various autoantibody [including rheumatoid factor (RF), anti-CCP2 antibody, antinuclear antibody, anti-dsDNA] and C-reactive protein status. All the tests were also performed in 26 age and sex-matched healthy controls. Estimation of antibodies was done by quantitative ELISA. IgM RF was positive in 47.89% cases (p value = 0.000), followed by IgG RF (42.01%, p = 0.000) and IgA RF (36.97%, p = 0.000). RF was positive in 64.7% RA cases (p value = 0.000) when all three isotypes were tested together. RF was also detected in one healthy control. In 92 cases, anti-CCP2 Ab was done, hence other data were analyzed further in 92 cases only. Anti-CCP2 Ab was positive (cut-off = 15.0 U/ml) in only 50% RA patients but none of the healthy controls was positive for it. Swelling of joints was seen in 82.6% anti-CCP2 Ab positive cases (p value = 0.092) when compared with anti-CCP2 Ab negative cases (67.4%) while among RF positive cases, only 65.4% ((p value = 0.010) cases had swelling of joints. Out of 39 RA cases presenting with disease duration less than 1 year, only 48.71% patients were anti-CCP2 Ab positive while RF was positive in 61.53% patients. Utility of various combined autoantibody tests revealed that if one does all isotypes of RF (IgG, IgA and IgM) only, then 64.7% RA cases can be diagnosed and if anti-CCP2 Ab is added to it, the sensitivity increases to 75.56%. Thus, our study concludes that anti-CCP2 Ab is not a sensitive test for the diagnosis of RA neither it is useful in early diagnosis of RA, but it increases the sensitivity if added with all RF isotypes.     

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.     

Rheumatoid factor and antibodies to cyclic citrullinated Peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis

OBJECTIVE: To study the diagnostic value of IgM rheumatoid factor (RF), IgA-RF, antibodies to cyclic citrullinated peptide (anti-CCP), and combinations of these antibodies, measured at baseline, to discriminate rheumatoid arthritis (RA) from undifferentiated polyarthritis (uPA) in patients with recent onset arthritis. METHODS: Patients with early arthritis with peripheral arthritis of 2 or more joints and symptom duration less than 3 years were clinically diagnosed as having RA or uPA by an experienced rheumatologist during the first year. Patients with bacterial, psoriatic, or crystal induced arthritis or spondyloarthropathy were excluded. Optimal cutoff values for serum IgM RF, IgA RF, and anti-CCP were deduced from receiver operating characteristics curves in order to predict the diagnosis of RA in early arthritis. RESULTS: A total of 379 patients (69% female, median age 57 yrs, range 17-86 yrs) were studied; 258 patients were clinically diagnosed as RA and 121 as uPA. Both IgM-RF > 40 IU/ml and anti-CCP > 50 AU/ml showed high specificity, but the sensitivity of these tests was low. In many RA patients the occurrence of IgM-RF and anti-CCP antibodies was independent. Thus the optimal criterion proved to be the combination of IgM-RF > 40 or anti-CCP > 50, which yielded sensitivity of 55.4% and specificity of 96.7%. CONCLUSION: The criterion IgM-RF > 40 or anti-CCP > 50 is able to predict the diagnosis of RA in early arthritis patients with high specificity and acceptable sensitivity. Anti-CCP testing combined with IgM-RF testing has additional value over IgM-RF testing alone in patients with early undifferentiated oligo and polyarthritis.     

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.     

Usefulness of anti-CCP antibodies in patients with hepatitis C virus infection with or without arthritis,rheumatoid factor,or cryoglobulinemia

The presence of antibodies to cyclic citrullinated peptide (CCP) has high specificity in the diagnosis of rheumatoid arthritis (RA). Hepatitis C virus (HCV) infection may induce extra-hepatic manifestations, such as polyarthritis that mimic RA. The aim of this study was to determine the prevalence of anti-CCP antibodies in HCV-infected patients with or without arthritis, rheumatoid factor (RF), or cryoglobulinemia and to investigate whether anti-CCP antibodies may be helpful in discriminating patients with RA from patients with HCV-associated arthropathy. A total of 44 patients with RA, 34 patients with HCV infections, and 42 control patients with non-RA rheumatic diseases were recruited for the study. Anti-CCP antibody levels were determined by enzyme-linked immunosorbent assay. We found that, consistent with other reports, patients with RA were more likely to have high titers of anti-CCP antibody than HCV-infected or control patients. A significant number of HCV-infected patients with neither RF nor cryoglobulinemia were also positive for anti-CCP antibodies (the three positive values were 36.10, 8.65, and 5.83 U/ml, P < 0.01 compared with the control patients). The presence of cryoglobulinemia and/or RF in HCV-infected patients did not affect the anti-CCP outcomes. Although anti-CCP antibodies remain to be a very useful tool in discriminating RA from non-RA, HCV-infected patients with neither RF nor cryoglobulinemia may have anti-CCP antibodies. Because of limited patient numbers, this tentative conclusion may need further confirmation with inclusion of more patient population.     

Positive anti-cyclic citrullinated proteins and rheumatoid factor during active lung tuberculosis

OBJECTIVES: To determine the prevalence of anti-cyclic citrullinated proteins (anti-CCP) and IgM rheumatoid factor (RF) in sera of patients with TB compared with healthy controls. PATIENTS AND METHODS: 47 consecutive patients with recently diagnosed active pulmonary TB and 39 healthy controls were studied. Data were collected by questionnaire on clinical features of the disease, duration of symptoms, fever, cough, arthralgia, myalgia, sicca symptoms. Serum samples were collected from patients before starting treatment for TB and frozen at -20 degrees C. Anti-CCP and IgM RF were evaluated by ELISA. RESULTS: The mean (SD) duration of TB related symptoms was 4.4 (1.7) months, 73% had fever, 94% a cough. Rheumatic symptoms were relatively rare: arthralgia (4%), myalgias (4%), eye and mouth dryness (2% and 9%, respectively). Mean (SD) levels of anti-CCP were significantly increased in patients with TB compared with controls: 44.9 (51) IU v 20 (7.3) IU (p = 0.002). Serum levels >40 U were found in 15/47 (32%) patients compared with 1/39 (2.6%) controls (p = 0.002). Mean (SD) serum levels of IgM RF were significantly increased in patients with TB: 17.8 (19) v 4.3 (5) (p<0.0001). IgM RF was positive (>6 IU) in 29/47 (62%) patients v 1/39 (2.6%) controls (p<0.0001). CONCLUSIONS: A significant proportion of patients with active TB have an increased titre of anti-CCP and IgM RF.     

Low serum level of COMP,a cartilage turnover marker,predicts rapid and high ACR70 response to adalimumab therapy in rheumatoid arthritis

The aim of this study was to evaluate serum biomarkers, used in clinical routine, to predict the American College of Rheumatology (ACR) response to long-term anti-TNF alpha treatment (adalimumab). Sera from 29 consecutive rheumatoid arthritis patients were analysed for anti-cyclic citrullinated peptide (anti-CCP), cartilage oligomeric matrix protein (COMP) and IgM and IgA RFs (class-specific rheumatoid factors) at the start of treatment with adalimumab and after 3, 6 and 12 months. The response to the therapy was evaluated by ACR 20, 50, 70 and by DAS 28 scores. The mean serum COMP level of the population did not change after treatment. However, patients with low serum COMP levels (<10 U/l) at baseline showed a significant (p<0.02) higher ACR70 response (>50%) within 3 months, and also at 6 months, than patients with higher COMP values (ACR70<20%). This was also reflected by significantly higher decrease in DAS score at 3 (p<0.02) and 6 months (p<0.01) treatments. The IgM RF titre decreased significantly (p=0.02) after the therapy, but the percentage of serum positivity for anti-CCP and IgA/IgM RF did not change. No significant correlation was shown between serum COMP levels and C-reactive protein/erythrocyte sedimentation rate during the follow-up. Neither were any correlations shown between ACR/DAS 28 scores and anti-CCP, Ig M/IgA RFs. Our data indicate that low (<10 U/l) serum COMP before starting anti-TNF alpha treatment predicts a rapid (within 3 months) and high ACR70 response compared to RA patients with higher COMP values. This might reflect different mechanisms in the cartilage process in the RA disease at that time of treatment with different therapeutic sensitivity to anti-TNF alpha treatment.     

Antibodies against cyclic citrullinated peptides in patients affected by rheumatoid arthritis before and after infliximab treatment

To evaluate antibodies against cyclic citrullinated peptides (anti-CCP) together with rheumatoid factor (RF), antinuclear antibodies (ANA) and C-reactive protein (CRP), in patients affected by rheumatoid arthritis (RA), before and after infliximab treatment. Twenty-seven patients (five men and 22 women, mean age of 51.9 years, mean duration of disease 12.6 years) affected by RA, refractory to conventional DMARDs, were treated with infliximab, at the conventional dosage. Before starting infliximab and after 22 weeks, on the occasion of the fifth infusion, anti-CCP antibodies were tested by ELISA method. At the same time IgM RF, ANA and CRP level were measured. Before infliximab therapy, anti-CCP antibodies resulted positive in 23 patients (85.1%); the serum level did not change after infliximab treatment; only one case negative at baseline became slightly positive after treatment. Before and after therapy RF resulted positive in 22 cases (81.4%) and 21 cases (77.7%) respectively; comparing values at baseline with those after 22 weeks of treatment with infliximab, RF levels significantly decreased, as well as CRP values. In contrast to both anti-CCP antibodies, which remained stable, and to RF, which fell after infliximab, ANA were positive 1: 160 in four cases at baseline and in 12 after treatment. The titre of anti-CCP antibodies did not significantly change after anti-TNF blocker administration; instead the positivity of RF significantly decreased. As opposed to antinuclear and anti-dsDNA antibodies, which may appear or increase in titre during infliximab treatment, the typical autoantibodies detectable in RA show a different trend; in fact, anti-CCP antibodies remained stable and RF decreased.     

Diagnostic potential of interleukin-40 (IL-40) in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is the most common type of inflammatory arthritis. Newly emerging evidence has highlighted the role of B-cell produced cytokines in the development and progression of RA. Specifically, the expression of IL-40 has been shown to be significantly increased in affected patients.Patients and methodsThe study included 66 patients attending Rheumatology Unit, Baghdad Teaching Hospital and 66 matched controls. C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were measured. Disease activity score (DAS28) was assessed. Serum IL-40 levels were assessed using an enzyme-linked immunosorbent assay (ELISA).ResultsThe mean ages of patients were 46.5 ± 10.2 years (23–68 years) and were 55 females and 11 males (F:M 5:1). 4 were smokers. Positivity of CRP, RF and anti-CCP were 75.8 %, 65.2 % and 62.2 % respectively. Steroids were received by 21.2 %, methotrexate by 56.1 %, biologics in the form of etanercept and adalimumab by 86.4 %. IL-40 was significantly higher in patients (9.1 ± 1.3 ng/ml) than in controls (7.5 ± 2.2 ng/ml; p < 0.001). The IL-40 level was comparable between females and males and was not related to smoking, CRP, RF or anti-CCP positivity or to receiving medications. Serum IL-40 showed good validity in diagnosing RA at a cut-off value (≥8.2 ng/ml) and area under curve (AUC) (0.74), the sensitivity was 73.2 %, specificity (66.7 %), and the accuracy (70.5 %)(p < 0.001).ConclusionThe increased level of serum IL-40 and its potential diagnostic role have been revealed in RA. Further studies are needed to be implement and elucidate the complete role of IL-40 in RA.     

类风湿关节炎患者血清中肿瘤坏死因子样配体1A的测定及临床意义

目的 检测类风湿关节炎(RA)患者血清中肿瘤坏死因子样配体1A(TL1A)的水平,分析 其在RA中的临床意义。方法 收集RA患者血清100例和健康对照者50名,采用双抗体夹心酶联免疫 吸附试验(ELISA)测定血清中TL1A水平,并分析血清TL1A水平与RA各临床和实验室指标的相关性, 计量资料,符合正态分布采用t检验,非正态分布采用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TL1A水平为(959±1146) pg/ml,显著高于健 康对照组[(529±154) pg/ml,t=3.683,P＜0.01];并且类风湿因子(RF)、隐性类风湿因子IgG( HRF-IgG)、抗 环瓜氨酸肽(CCP)抗体阳性组TL1A水平[分别为(962±1043)、(833±1104)、(908±1115) pg/ml]均高于阴 性组TLlA水平[分别为(628±343)、(576±134)、(628±4.01) pg/ml],差异有统计学意义(t=3.224,1.317,1.003; P均＜0.05)。另外,TLlA阳性组RA患者的RF、HRF-IgG以及抗CCP抗体阳性率(分别为90％、42％、 85％)均较TL1A阴性组患者（分别为56％、11％、33％）显著升高(x2=-0.372,-2.402,-2.774;P均＜0.05)。结 论TL1A在RA患者血清中表达增高,并与多种自身抗体（包括RF、HRF-IgG和抗CCP抗体）密切相关, 可能是RA预后不良因素之一。     

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。     

Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis

BACKGROUND: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria. OBJECTIVE: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis. METHODS: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone. RESULTS: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF >or=50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF >or=50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease. CONCLUSIONS: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.     

The relationship of serum calprotectin with disease activity,functional status,ultrasonographic findings and radiological damage in rheumatoid arthritis patients

Aim of the workTo measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) patients and to assess its association with disease activity, functional status, ultrasonographic findings, and radiological damage.Patients and methodsThis study included 47 RA patients and 33 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score (DAS28), health assessment questionnaire (HAQ), modified Larsen radiological score, musculoskeletal ultrasound and serum CLP levels were assessed.ResultsThe mean age of the patients was 42.5 ± 12.8 years; 34 females and 13 males (F:M 2.6:1) with a mean disease duration of 2.6 ± 1.1 years. RF was positive in 72%. CLP level was significantly increased in patients compared to control (2.78 ± 0.89 μg/ml vs. 0.84 ± 0.5 μg/ml; p < 0.001) and in those with activity (3.27 ± 0.75 μg/ml) compared to those in remission (1.92 ± 0.15 μg/ml). A significant correlation was detected between CLP and DAS28, ESR, CRP, HAQ, and modified Larsen scores (p < 0.001). On regression, tender and swollen joint counts, ESR, CRP, HAQ, modified Larsen, ultrasound 7 score and CLP level were significant predictors of activity but were insignificant on multivariate analysis. At a cut-off value of 2.35 μg /ml CLP can significantly differentiate active RA patients from those in remission (AUC 0.95; p < 0.001) at a sensitivity of 90%, specificity of 100%, and accuracy of 95%.ConclusionThe serum CLP levels were significantly high in RA patients and these high levels were associated with disease activity, functional status, ultrasonographic findings, and radiological damage.     

Diagnostic utility of the Elecsys anti-CCP assay in patients with rheumatoid arthritis

Abstract

Objective. The automatic anti-cyclic citrullinated peptide (anti-CCP) antibodies assay offered great advantages over traditional methods in terms of improved precision, reliability, technical simplicity, short turnaround time and high-speed throughput. In this study, we evaluated the main technical performance and diagnostic accuracy of the first automatic anti-CCP assay approved in China.

Methods. The study comprised 106 rheumatoid arthritis (RA) patients, 203 non-RA rheumatic disease controls and 46 healthy persons. Anti-CCP, rheumatoid factor (RF), α₁-acid glycoprotein, C-reactive protein and erythrocyte sedimentation rate were measured and compared. The precision, reference intervals for Chinese population and cut-off value for RA diagnosis, as well as the suitable diluent for anti-CCP were assessed. The positive rate and score of anti-CCP were compared with RF and acute-phase reactants, according to the new RA criteria.

Results. Within- and between-run imprecision, expressed as the coefficient of variation, were 0.47–1.36% and 1.15–2.63%, respectively. Upper 95% reference limit of anti-CCP in healthy Chinese was 8.8 U/mL. The area under curve of the receiver operating characteristic(ROC) for anti-CCP and RF were 0.882 (95% CI 0.833–0.930) and 0.844 (95% CI 0.792–0.897), respectively. Based on the cut-off value set by ROC, compared to RF, anti-CCP had higher sensitivity (96.8% vs. 78.3%) and specificity (90.9% vs. 70.7%). With 17 U/mL set as the optimal cut-off for anti-CCP, the total positivity of anti-CCP was comparable to that of RF (76.4% vs. 75.5%), but the high-positivity rate of anti-CCP was significantly higher (74.5% vs. 62.3%, p < 0.005).

Conclusions. Our results confirm anti-CCP as a more sensitive and specific marker than RF for the diagnosis of RA. The diagnostic performance of the Elecsys anti-CCP assay makes it a useful adjunct to clinical practice in the Chinese population.     

Absence of antibody to cyclic citrullinated peptide in sera of non-arthritic patients with chronic hepatitis B virus infection

The objective of this study was to investigate if antibody to cyclic citrullinated peptide (anti-CCP) is detected in sera of patients with chronic hepatitis B virus (HBV) infection. Serum anti-CCP and IgA, IgG, and IgM rheumatoid factor (RF) isotypes were measured by enzyme-linked immunosorbent assay on 176 non-arthritic patients with HBV infection. IgA RF, IgG RF, and IgM RF were detectable in 29.5, 21, and 18.8% of the tested sera, respectively, with a total seropositivity rate of 42.7%. Marginally elevated anti-CCP was detected in one patient (0.6%). By regression analysis, there was no statistically significant association between the serum levels of anti-CCP and serum IgA, IgG, or IgM RF (R ² = 0.033, with respective p values of 0.224, 0.297, and 0.334). In conclusion, anti-CCP was rarely detected in non-arthritic patients with HBV infection in contrast to RF. Thus, testing for anti-CCP may be a useful tool for the diagnosis of rheumatoid arthritis in this population.     

Clinical significance of serum B cell chemokine (CXCL13) in early rheumatoid arthritis patients

Background

The diagnosis of early rheumatoid arthritis (RA) is challenging. B-cell chemokine (CXCL13) plays a critical role in the disease pathogenesis.

High positivity of anti-CCP antibodies in patients with Down syndrome

The aim of the present study was to evaluate the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in patients with Down’s syndrome (DS) previously tested for IgM rheumatoid factor (RF) and to correlate the results with clinical findings. Eighty-eight patients with DS previously tested for IgM-RF were divided into two groups matched for sex and age. Group A consists of 42 RF positive patients and group B of 44 RF negative patients. The presence of anti-CCP antibody was determined using a second-generation enzyme-linked immunosorbent assay. A total of 52.3% (45/86) of DS patients were positive for anti-CCP antibodies. Twenty-four patients (57.1%) of the RF positive group and 21 (47.7%) of the RF negative group presented anti-CCP circulating antibodies. The concordance between both tests was 54.6%. None of the patients had clinical evidence of rheumatoid arthritis or juvenile idiopathic arthritis. Although a high prevalence of anti-CCP antibodies was observed in DS patients, no association has been found presently with clinical disease. Careful follow-up of these patients will be necessary to clarify the real significance of these findings.