Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti–cyclic citrullinated peptide antibody

Objective

To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti‐CCP) antibody levels among patients with rheumatoid arthritis (RA).

Methods

The study sample included 66 RA patients who completed double‐blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti‐CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels.

Results

Patients had a mean ± SD age of 49.9 ± 12.0 years and were predominantly female (n = 51; 77%). The mean ± SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 ± 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a ≥25% reduction in the anti‐CCP antibody level during the course of treatment, and 35 patients (55%) had a ≥25% reduction in RF. After adjustment for the baseline anti‐CCP antibody level, only a shorter disease duration (≤12 months) was significantly associated with a decline in the level of anti‐CCP antibody (OR 3.0, 95% CI 1.0–8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2–10.4).

Conclusion

Shorter disease duration predicts greater declines in anti‐CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti‐CCP antibody level.

     

血清抗角蛋白抗体抗环瓜氨酸肽抗体和类风湿因子在类风湿关节炎中的意义

目的 评价抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)中的意义.方法 收集82例RA患者及56例非RA患者,测定其抗CCP抗体、AKA和RF水平,评价对RA诊断的敏感性、特异性,比较RA患者中抗CCP抗体、AKA阳性组和阴性组的压痛关节数、肿胀关节数、红细胞沉降率(ESR)、C反应蛋白(CRP)、疾病活动指数(DAS)、Ritchie's指数(RAI).结果 单独检测AKA、抗CCP抗体、RF及联合检测的曲线下面积都较高(P<0.05).抗CCP抗体、AKA的特异度分别为92.9%、91.1%,联合检测AKA、抗CCP抗体和RF有任何一种及以上阳性的灵敏度最高,为95.1%.抗CCP抗体阳性组与阴性组的关节肿胀数、关节压痛数、ESR、CRP、DAS、RAI差异有统计学意义(P<0.05);AKA阳性组与阴性组的关节肿胀数、ESR、DSA差异均有统计学意义(P<0.05).结论 联合检测抗CCP抗体、RF、AKA对诊断RA有意义,抗CCP抗体、AKA可能与RA的活动度相关.     

抗环瓜氨酸肽抗体滴度变化与类风湿关节炎患者达标和复发的相关性研究

目的:探究抗CCP抗体滴度与RA疾病活动度、达标和复发的相关性。方法:选取北京大学第一医院风湿免疫科RA随访队列中的患者,入组患者需在我院首次就诊时抗CCP抗体阳性,且间隔至少1年随访过程中有至少1次抗CCP抗体复查结果。根据随访过程中抗CCP抗体滴度自基线下降是否超过10%,将患者分为下降组和未下降组,采用单因素比较...     

Relation of rheumatoid factor and anti-cyclic citrullinated peptide antibody with disease activity in rheumatoid arthritis: cross-sectional study

To analyze the association of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) with non-remission and with disease activity measures in rheumatoid arthritis (RA). Cross-sectional study of consecutive RA patients. Non-remission was defined as a disease activity score (DAS28) ≥2.6 at study enrollment. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were additionally measured. Serum titers of RF and anti-CCP were transformed into incremental levels (100/units) and log-transformed levels. Analysis of association with non-remission was done with logistic regression models, with and without adjustment for age, sex, disease duration, and corticoid use. Multiple regression models, raw and similarly adjusted, were used to measure the association of RF and anti-CCP with the disease activity measures. A total of 385 patients were included, of whom 286 (74 %) were not in remission. Log-transformed RF level was associated with an increased risk of non-remission after adjustment (OR = 1.32, 95 % CI 1.04–1.67). This association was especially evident in patients with less than 10 years of disease duration (OR = 1.51, 95 % CI 1.15–1.99) and in those using steroids (OR = 2.06, 95 % CI 1.22–3.48). Serum RF titers and log-transformed RF levels showed a small but significant association with DAS28 score (adjusted beta coefficients 0.002 and 0.18, respectively; both p ≤ 0.01), but neither with SDAI or CDAI nor with anti-CCP antibody. : Log-transformed RF levels might be associated with non-remission in RA, especially in patients with short disease duration or on steroids.     

Association of HLA-DR3 with anti-cyclic citrullinated peptide antibody-negative rheumatoid arthritis

OBJECTIVE: Recent data have shown that the most prominent and longest known genetic risk factors for rheumatoid arthritis (RA), HLA-DRB1 shared epitope alleles, are only associated with RA that is characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and not with anti-CCP-negative RA. We undertook this study to investigate whether anti-CCP-negative RA is associated with other HLA-DRB1 alleles. METHODS: HLA typing was performed for 377 patients from the Leiden Early Arthritis Clinic who were diagnosed as having RA within the first year of followup (206 anti-CCP-positive patients and 171 anti-CCP-negative patients), 235 patients who, after 1 year, had undifferentiated arthritis (UA) (28 anti-CCP-positive patients and 207 anti-CCP-negative patients), and 423 healthy control subjects. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for HLA-DRB1 allele frequencies were determined for all patient groups compared with the healthy control group. RESULTS: HLA-DR3 was more frequently present in the anti-CCP-negative RA group than in the control group (OR 1.84, 95% CI 1.26-2.67). This was not the case for anti-CCP-positive RA (OR 0.92, 95% CI 0.60-1.40). HLA-DR3 was also more frequently present in anti-CCP-negative UA patients (OR 1.59, 95% CI 1.10-2.28), but not in anti-CCP-positive UA patients (OR 0.68, 95% CI 0.17-1.92). CONCLUSION: HLA-DR3 is associated with anti-CCP-negative arthritis and not with anti-CCP-positive arthritis. These data show that distinct genetic risk factors are associated with the presence of anti-CCP antibodies in RA and indicate that different pathogenetic mechanisms underlie anti-CCP-positive and anti-CCP-negative RA.     

Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease

Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2 % of RA patients and 0 % of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5 % of RA patients and 42 % of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.     

A retrospective study of the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis

OBJECTIVE: To investigate the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody (anti-CCP) retrospectively in patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-CCP were measured retrospectively in 131 patients with RA and 90 patients with non-RA rheumatic diseases using a commercially available kit. All sera were collected from patients during the 22-year period, 1982-2004. To analyze the fluctuation in anti-CCP levels, 17 RA patients were selected on the basis of showing a significantly higher anti-CCP level in a serum sample taken at the first visit (> 80 U/ml), and availability of preserved serum samples that had been taken from each patient at 10 time points. RESULTS: The test gave a sensitivity of 88% (115/131) and a specificity of 81% (73/90). The longitudinal study of 17 RA patients showed that anti-CCP levels were elevated at the first visit in 12 (71%) patients and then decreased gradually, whereas those in the other five (29%) patients fluctuated substantially. In both cases, anti-CCP levels tended to fluctuate in parallel with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, reflecting the spontaneous aggravation of arthritis and the efficacy of anti-rheumatic drugs. The courses of three representative RA patients are illustrated in detail along with their therapeutic regimens, and these further confirm the correlation of anti-CCP levels with laboratory parameters (ESR and CRP) as well as the activity of arthritis. CONCLUSION: Measurement of serum anti-CCP levels was found to be useful for not only the diagnosis but also the management of RA.     

抗环瓜氨酸肽抗体检测在类风湿关节炎中的意义

目的 检测抗环瓜氨酸肽（CCP）抗体在类风湿关节炎（RA）中的阳性率,探讨抗CCP抗体检测在RA中的意义。方法 以根据已知cDNA序列人工合成的CCP为抗原建立ELISA方法检测294例RA,132例其他风湿性疾病,135例非风湿性疾病中的抗CCP抗体的分布。比较抗CCP抗体与抗核周因子（APF）、抗角蛋白抗体（AKA）、类风湿因子（RF）以及HLA－DR4的相关性。结果 294例RA病人中,抗CCP抗体的阳性率为46．6％,其他风湿性疾病的阳性率为5．3％,非风湿性疾病的阳性率为1．5％。抗CCP抗体对RA的敏感性和特异性分别为46．6％,96．6％。抗CCP抗体与APF、AKA以及HLA－DR4之间有相关性,与RF之间无相关性。结论 抗CCP抗体对RA具有良好的敏感性（46．6％）和特异性（96．6％）,能用于RA的诊断。抗CCP抗体与AFP、AKA有相关性,但不完全重叠。抗CCP抗体可视为RA新的血清学诊断指标。     

抗CCP抗体和抗Sa抗体联合检测对老年人RA的临床意义

目的探讨抗环瓜氨酸肽抗体（抗CCP抗体）和抗Sa抗体联合检测对老年人类风湿关节炎（RA）的临床意义。方法检测85例老年人RA患者的抗CCP抗体和抗Sa抗体,结合临床资料分析。结果抗CCP抗体和抗Sa抗体对RA诊断敏感性分别为77．6％和32．9％,特异性分别为97．4％和95．4％。抗CCP抗体、抗Sa抗体、类风湿因子（RF）均阳性组医生对病情评估、患者对病情评估、Sharp评分、ESR及CRP水平均较阴性组增高。24例RF阴性老年人RA中,抗CCP抗体、抗Sa抗体阳性率分别为50％、41．7％。结论抗CCP抗体和抗Sa抗体联合检测有助于老年人RA的诊断,且二者与患者病情活动性及严重性相关。     

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。     

抗环瓜氨酸肽抗体与类风湿关节炎的相关性研究

目的 研究类风湿关节炎（RA）患者抗环瓜氨酸肽抗体（CCP抗体）与肿瘤坏死因子（TNF）-α、类风湿因子（RF）、红细胞沉降率（ESR）、血小板计数（PLT）及临床的相关性，以及未分类关节炎（痛）患者6个月后随访转归情况，探讨其在RA早期诊断及发病机制中的意义。方法 对91例RA患者，46例未分类关节炎（痛）患者，45例其他风湿病患者，应用酶联免疫吸附试验（ELISA）法检测血清抗CCP抗体、TNF—α，速率散射免疫比浊法检测RF。结果 RA组及未分类关节炎（痛）组患者外周血抗CCP抗体水平与TNF—α水平、PLT、关节肿胀度呈显著正相关（r=0．854，P=0．000；r=0．882，P=0．000；r=0．318，P=0．002；r=0．486，P=0．001；r=0．291，P=0．005；r=0．731，P=0．000），RA组及未分类关节炎（痛）组患者外周血抗CCP抗体水平分别与握力呈弱负相关（r=-0．228，P=0．030）、与ESR呈弱正相关（r=0．365，P=0．013）；RA组及未分类关节炎（痛）组患者外周血抗CCP抗体水平明显高于其他风湿病组患者（P=0．000）；其他风湿病组患者外周血抗CCP抗体水平高于正常组对照组（P=0.011）。46例未分类关节炎（痛）组患者有24例抗CCP抗体阳性，6个月后随访，有32例为早期RA，抗CCP抗体在早期RA的阳性率为72％（23／32），96％（23／24）的未分类关节炎（痛）组抗CCP抗体阳性患者为早期RA.结论 抗CCP抗体反映了RA一定的病情活动性；可用于RA早期诊断及利于早期RA的鉴别诊断；抗CCP抗体水平升高，伴有TNF—α、ESR、PLT升高及关节肿胀时，有助于RA早期诊断。