[EULAR文摘] 在总人群中监测ACPA能否预测早期关节炎

标签: 类风湿关节炎; 抗CCP抗体; 预测因子; 病程演变

在总人群中监测ACPA能否预测早期关节炎

Verstappen SM, et al. EULAR 2015. Present ID: OP0268.

背景：ACPA免疫应答常常先于RA诊断数年, 鲜有研究比较正常人群的ACPA与已发展为RA或炎性多关节炎(IP)人群中的ACPA。

目的：正常人群ACPA状态与将来发展RA或炎性多关节炎(IP)人群的ACPA状态进行比较。

方法：用ELISA方法检测ACPA(欧洲Diagnostica公司)。基线时的血清样本来自在英国诺福克进行的欧洲癌症前瞻性调查研究(EPIC-Norfolk)队列。此外, 资料包括ACPA状态(>25U /mL为阳性)、年龄、性别、社会经济地位(如手工/非技术熟练的工人, 经理/技术熟练的非体力劳动者, 专业人员)和吸烟状况(从未吸烟、曾经和现在)。这个人群中若有发展为IP/RA的患者, 将通过诺福克关节炎注册登记中心(NOAR, 英国一个基于初级保健的队列)而被找到。用逻辑回归分析评估总人群的人口统计特征是否与ACPA+的关联, 校正年龄和性别后用Cox回归分析评估ACPA与IP之间的关联性。在EPIC-Norfolk队列登记注册时已经有关节炎症状的患者将不被纳入本次Cox回归分析(N= 104)。此外, 还分析了ACPA与吸烟之间的相互作用。随访患者直至出现以下任何一种情况, 他/她们发展为IP/RA, 或截尾至死亡或2014年5月。

结果：18628例EPIC参与者基线时检测了ACPA, 年龄为40-79岁。EPIC人群中有429例(2.30％)ACPA阳性者。EPIC人群中有104例在注册时已是IP/RA患者(35.6％ ACPA+, 滴度中位数6.95 [IQR: 3.75 -121.2])。在311051病人年随访过程中中, 173人发展为IP。

横断面分析显示, 曾经吸烟和现在吸烟分别与ACPA+呈正相关(OR: 1.60, 95％CI: 1.95-2.13; OR: 1.29, 95％CI:1.02-1.55), 年龄与ACPA+相关(OR: 1.01, 95％CI: 1.00-1.03)。患者性别、社会地位与ACPA无关。上述173例在随访过程中发展为IP, 并在NOAR注册登记, 其中85例(49.4％)符合2010年ACR/EULAR分类标准。基线ACPA检测结果是发展为IP/RA的预测因素(校正HR: 10.3, 95%CI: 6.90-15.34)。ACPA与吸烟之间的交互作用不明显。

结论：40至79岁的总人群样本中ACPA阳性率为2.1％。ACPA阳性者在3至10年后发展为IP/ RA的可能性是ACPA阴性者的10倍。ACPA联合其它检查可有效地找到IP/RA高风险人群。

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原文链接或参见以下信息。

Ann Rheum Dis 2015;74:173 doi:10.1136/annrheumdis-2015-eular.4793

• Oral Presentations

OP0268 Anti-Citrullinated Protein Antibody (ACPA) Status in the General Population and as a Predictor of Future Inflammatory Polyarthritis: The EPIC-2-Noar Study

1. S.M. Verstappen¹, 
2. J.C. Sergeant², 
3. R.N. Luben³, 
4. A. Bhaniani³, 
5. S. Anuj³, 
6. A. MacGregor⁴,
7. N. Wareham³, 
8. D.P. Symmons^1,2, 
9. K.T. Khaw³, 
10. I.N. Bruce^1,2 
11. on behalf of RA-MAP consortium

-Author Affiliations

1. ¹Arthritis Research UK Centre for Epidemiology, The University of Manchester
2. ²NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester
3. ³European Prospective Investigation into Cancer and Nutrition, Department of Public Health and Primary Care, Cambridge
4. ⁴Norfolk and Norwich University Hospital, Norwich, United Kingdom

Abstract

           

Background Anti-citrullinated protein antibody (ACPA) immune response occurs several years prior to the diagnosis of rheumatoid arthritis (RA). However, limited data are available on ACPA status in the general population compared to those who develop RA or inflammatory polyarthritis (IP) in the future.

Objectives The aim of this study was to examine ACPA status in the general population and in patients developing IP/RA.

Methods ACPA was measured by ELISA (Euro-Diagnostica) in stored serum samples collected at baseline in people participating in the European Prospective Investigation of Cancer in Norfolk, (EPIC-Norfolk), a prospective population-based study in the UK. In addition, data on ACPA status (positive >25 U/ml) age, gender, socio-economic status (i.e. manual/unskilled worker, manager/skilled non-manual worker, professional), smoking status (i.e. never, former, current) were also collected at inclusion. Individuals who subsequently developed IP/RA were identified by linkage with the Norfolk Arthritis Register (NOAR), a primary-care based cohort with an overlapping catchment area in the UK. Logistic regression analyses were used to assess the association between demographic characteristics and ACPA positivity in the general population. Cox regression analyses were performed to assess the association between ACPA and the development of IP, adjusting for age and gender. Patients with a symptom onset prior to inclusion in EPIC-Norfolk were excluded from the Cox regression analysis (N=104). In addition, the interaction between ACPA and smoking was tested. People were followed until development of IP/RA or censored at date of death or May 2014, whichever came first.

Results ACPA was measured in 18,628 EPIC participants aged 40-79 years. ACPA was positive in 429 subjects (2.30%) of the whole EPIC population including 104 patients with prevalent IP/RA (35.6% ACPA positive, median titre 6.95 [IQR 3.75 – 121.2] U/ml) and 173 (16.8% ACPA positive, median titre 5.14 [IQR 3.37 – 9.41] U/ml) subjects who developed IP during 311,051 person years of follow-up. Cross-sectionally, current and former smokers (OR 1.60, 95%CI 1.95 to 2.13 and OR 1.29 95%CI 1.02 to 1.55, respectively) and older age (OR 1.01 95%CI 1.00 to 1.03) were associated with ACPA positivity. Gender and socio-economic status were not associated with ACPA. Of 173 patients who developed IP and were notified to NOAR, 85 (49.4%) fulfilled the 2010 ACR/EULAR criteria for RA at entry to the NOAR cohort. ACPA status was predictive for the development of IP/RA (adjHR 10,3 95%CI 6.90 to 15.34). The interaction between ACPA and smoking was not significant.

Conclusions ACPA was positive in 2.1% of a general population sample aged 40-79 years old. People who were ACPA positive were 10 times more likely to develop IP/RA in the next 3-10 years than those ACPA negative subjects. ACPA may be a useful adjunct to other screening approaches to identify people at higher risk of developing IP/RA.