中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
  • BA、CA收录

中国医科大学学报 ›› 2019, Vol. 48 ›› Issue (1): 39-43.doi: 10.12007/j.issn.0258-4646.2019.01.008

• 论著 • 上一篇    下一篇

抗氨甲酰化蛋白抗体检测在类风湿关节炎中的意义

黄睿, 张宁   

  1. 中国医科大学附属盛京医院第二风湿免疫科, 沈阳 110004
  • 收稿日期:2018-03-26 出版日期:2019-01-30 发布日期:2019-01-05
  • 通讯作者: 张宁 E-mail:zhangning@sj-hospital.org
  • 作者简介:黄睿(1989-),女,医师,硕士.
  • 基金资助:
    辽宁省自然科学基金(2014021081);沈阳市科技计划(1801220)

Significance of Anti-carbamylated Protein Antibody Measurement in the Diagnosis of Rheumatoid Arthritis

HUANG Rui, ZHANG Ning   

  1. Department of Rheumatology, Shengjing Hospital, China Medical University, Shenyang 110004, China
  • Received:2018-03-26 Online:2019-01-30 Published:2019-01-05

摘要: 目的 探究类风湿关节炎(RA)患者中检测血清抗氨甲酰化蛋白(CarP)抗体的意义和应用价值。方法 选取我院风湿免疫科2014年9月至2015年10月收治的RA初诊患者135例(RA组),同时选取健康体检者85例作为对照组(健康组),采用ELISA方法分别测定患者血清中抗CarP抗体、抗环瓜氨酸多肽(CCP)抗体的水平,并详细记录每例患者肿胀关节数、压痛关节数、红细胞沉降率(ESR)、C反应蛋白(CRP)等临床观察指标。分析并比较抗CarP抗体与抗CCP抗体之间以及与各种临床指标的相关性,初步探讨定量测定抗CarP抗体、抗CCP抗体的水平与疾病活动度和影像学改变的关系。结果 本研究纳入的135例RA初诊患者中,抗CCP抗体阳性者106例(78.5%),抗CarP抗体阳性者67例(49.6%)。联合检测抗CCP抗体和抗CarP抗体可提高诊断的特异性,高达97.6%。抗CarP抗体水平与患者肿胀关节数、压痛关节数、DAS28评分呈显著正相关(r=0.61,P=0.001;r=0.67,P=0.001;r=0.62,P=0.001),与CRP、ESR呈弱正相关(r=0.28,P=0.015;r=0.35,P=0.018),与病程(r=0.09,P=0.43)无相关性。135例RA患者中98例(72.6%)存在放射学改变,37例(27.4%)未出现放射学改变,依照X线片改变显示的不同关节损伤程度分期,血清中2种抗体水平的差异有统计学意义(P<0.05)。结论 联合检测抗CarP抗体和抗CCP抗体可提高诊断的特异性。抗CarP抗体可能与RA患者的病情活动度和骨质破坏相关,有望成为RA患者新的诊断、判断患者病情活动和预后的重要指标。

关键词: 抗环瓜氨酸多肽抗体, 抗氨甲酰化蛋白抗体, 类风湿关节炎

Abstract: Objective To explore the significance of serum anti-carbamylated protein (anti-CarP) antibody measurement for diagnosing rheumatoid arthritis (RA). Methods In this study,135 patients with newly diagnosed RA (RA group) and 85 healthy subjects (healthy group) were enrolled. ELISA was performed to measure anti-CarP and anti-cyclic citrullinated peptide (anti-CCP) antibodies. The numbers of swollen and tender joints,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) level were recorded. Results Anti-CCP antibody was positive in 106 cases (78.5%) and anti-CarP antibody was positive in 67 cases (49.6%) in the RA group. The sensitivity of combined measurement of anti-CCP and anti-CarP antibodies can improve the specificity of diagnosis,up to 97.6%. Among cases of anti-CarP antibody positivity,the number of swollen and tender joints and DAS-28 score were positively correlated with anti-CarP antibody level (r=0.61,P=0.001;r=0.67,P=0.001;r=0.62,P=0.001,respectively) and weakly correlated with CRP level and ESR (r=0.28,P=0.015;r=0.35,P=0.018,respectively),but not correlated with disease duration (r=0.09,P=0.43). A total of 98 cases (72.6%) had radiological changes. At different levels of joint damage severity observed on radiographs,the differences between serum anti-CarP and anti-CCP antibody levels were statistically significant (P<0.05). Conclusion Combined detection of anti-CarP and anti-CCP antibodies increases diagnostic specificity for RA. Anti-CarP antibody level is also correlated with severity of joint damage,implicating its involvement in the development and progression of RA. It may become an important marker for RA diagnosis,severity evaluation,and prognosis prediction.

Key words: anti-circle citrullinated peptide antibody, anti-carbamylated protein antibody, rheumatoid arthritis

中图分类号: 

  • R593.22
[1] SCOTT DL,WOLFE F,HUIZINGA TW. Rheumatoid arthritis[J]. Lancet,2010,376(9746):1094-1108. DOI:10.1016/S0140-6736(10) 60826-4.
[2] KOKKONEN H,MULLAZEHI M,BERGLIN E,et al. Antibodies of IgG,IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis[J]. Arthritis Res Ther,2011,13(1):R13. DOI:10.1186/ar3237.
[3] VAN VENROOIJ WJ,VAN BEERS JJ,PRUIJN GJ. Anti-CCP antibodies:the past,the present and the future[J]. Nat Rev Rheumatol,2011,7(7):391-398. DOI:10.1038/nrrheum.2011.76.
[4] WILLEMZE A,TOES RE,HUIZINGA TW,et al. New biomarkers in rheumatoid arthritis[J]. Neth J Med,2012,70(9):392-399.
[5] ALETAHA D,NEOGI T,SILMAN AJ,et al. 2010 rheumatoid arthritis classification criteria:an American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Ann Rheum Dis,2010,69(9):1580-1588. DOI:10.1002/art.27584.
[6] DE ROOY DP,KALVESTEN J,HUIZINGA TW,et al. Loss of metacarpal bone density predicts RA development in recent-onset arthritis[J]. Rheumatology,2012,51(6):1037-1041. DOI:10.1093/rheumatology/ker43.
[7] VAN KUIJK AW,TAK PP. Synovitis in psoriatic arthritis:immunohistochemistry,comparisons with rheumatoid arthritis,and effects of therapy[J]. Curr Rheumatol Rep,2011,13(4):353-359. DOI:10.1007/s11926-011-0181-y.
[8] SHI J,VAN DE STADT LA,LEVARHT EW,et al. Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis[J]. Ann Rheum Dis,2014,73(4):780-783. DOI:10.1136/annrheumdis-2013-204154.
[9] WⅡK AS,VENROOIJ WJ,PRUIJN GJ. All you wanted to know about anti-CCP but were afraid to ask[J]. Autoimmuny Rev,2010,10(2):90-93. DOI:10.1016/j.autrev.2010.08.009.
[10] WILLEMZE A,TROUW LA,TOES RE,et al. The influence of ACPA status and characteristics on the course of RA[J]. Nat Rev Rheumatol,2012,8(3):144-152. DOI:10.1038/nrrheum.2011.204.
[11] WILLEMZE A,TOES RE,HUIZINGA TW,et al. New biomarkers in rheumatoid arthritis[J]. Neth J Med,2012,70(9):392-399.
[12] BRINK M,VERHEUL MK,RÖNNELID J,et al. Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis,their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage[J]. Arthritis Res Ther,2015,17:25. DOI:10.1186/s13075-015-0536-2.
[13] SCINOCCA M,BELL D,POPE J,et al. Antihomocitrullinated fibrinogen antibodies are specific to rheumatoid arthritis and frequently bind citrullinated proteins/peptides[J]. Arthritis Rheum,2011,63(11):850. DOI:10.3899/jrheum.130742.
[14] GAN RW,TROUW LA,SHI J,et al. Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are associated with its future diagnosis[J]. J Rheumatol,2015,42(4):572. DOI:10.3899/jrheum.140767.
[15] AJEGANOVA S,HUIZINGA TW. Rheumatoid arthritis:seronegative and seropositive RA:alike but different?[J]. Nat Rev Rheumatol,2015,11(1):8-9. DOI:10.1038/nrrheum.2014.194.
[16] SHI J,WILLEMZE A,JANSSEN GM,et al. Recognition of citrullinated and carbamylated proteins by human antibodies:specificity,cross-reactivity and the ‘AMC-Senshu’ method[J]. Ann Rheum Dis,2013,72(1):148-150. DOI:10.1136/annrheumdis-2012-201559.
[17] SHI J,KNEVEL R,SUWANNALAI P,et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage[J]. Proc Natl Acad Sci USA,2011,108(42):17372-17377. DOI:10.1073/pnas.1114465108.
[18] SHI J,VAN STEENBERGEN HW,VAN NIES JA,et al. The specificity of anti-carbamylated protein antibodies for rheumatoid arthritis in a setting of early arthritis[J]. Arthritis Res Ther,2015,17:339. DOI:10.1186/s13075-015-0860-6.
[19] IOAN-FACSINAY A,EL-BANNOUDI H,SCHERER HU,et al. Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities[J]. Ann Rheum Dis,2011,70(1):188-1893. DOI:10.1136/ard.2010.131102.
[1] 姜薇, 王娟. 血清白细胞介素-6和白细胞介素-1β水平在预测依那西普治疗类风湿关节炎患者临床应答中的作用[J]. 中国医科大学学报, 2019, 48(2): 175-179,183.
[2] 韩俊, 张英. 血清生存素水平在预测肿瘤坏死因子-α抑制剂治疗类风湿关节炎临床疗效中的作用[J]. 中国医科大学学报, 2019, 48(2): 153-158.
[3] 方芳, 丁爽, 吴春玲, 段宏梅, 刘海娜, 肖卫国. Noggin阻断BMP-7/Smad信号通路对类风湿关节炎成纤维样滑膜细胞增殖及IL-6、IL-8表达的影响[J]. 中国医科大学学报, 2018, 47(9): 816-819.
[4] 范晓蕾, 刘中华, 岳涛, 何东仪. 血清TNF-α、IL-1β、IL-6和IL-17表达水平在阿达木单抗治疗活动性类风湿关节炎中的疗效预测作用[J]. 中国医科大学学报, 2018, 47(6): 556-561.
[5] 赵滢, 王晓非. 1 757例住院类风湿关节炎患者临床特点分析[J]. 中国医科大学学报, 2018, 47(12): 1107-1110,1115.
[6] 于婷婷, 张宁. 类风湿关节炎患者甲状腺相关抗体的临床分析[J]. 中国医科大学学报, 2018, 47(1): 32-35.
[7] 赵琳,徐京京,王晓非,张晓莉. 类风湿关节炎合并牙周疾病患者的 IL-17A 表达[J]. 中国医科大学学报, 2016, 45(12): 1115-1118.
[8] 宋颖,高薇,刘义. 抗骨桥蛋白抗体对胶原诱导大鼠类风湿关节炎作用的研究[J]. 中国医科大学学报, 2015, 44(5): 405-410.
[9] 教婷,张宁. 类风湿关节炎患者血清C-X-C配体10与疾病的相关性[J]. 中国医科大学学报, 2015, 44(11): 992-994.
[10] 崔东源, 王晓非. CCL17在类风湿关节炎患者外周血清中的表达及意义[J]. 中国医科大学学报, 2015, 44(10): 913-916.
[11] 方芳,袁红霞,丁爽,段宏梅,吴春玲,刘海娜,肖卫国. 类风湿关节炎患者血清骨形态发生蛋白7的水平及临床意义[J]. 中国医科大学学报, 2014, 43(9): 814-817.
[12] 陈欢雪,王晓非. 白细胞介素37在类风湿关节炎发病机制中的作用[J]. 中国医科大学学报, 2014, 43(3): 275-276.
[13] 尹春香,王晓非. 类风湿关节炎患者干扰素调节因子4基因表达变化的研究[J]. 中国医科大学学报, 2013, 42(11): 1019-1021.
[14] 田百玲, 刘旭东, 吴春玲, 杨娉婷, 肖卫国. 绝经后女性类风湿关节炎患者骨密度与生化免疫指标相关性的研究[J]. 中国医科大学学报, 2012, 41(2): 139-142.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 于雪馨, 王常林, 孙荣国, 杨屹. 鼠输尿管完全梗阻后肾脏病理及足细胞表型改变的研究[J]. 中国医科大学学报, 2010, 39(1): 1 .
[2] 王新利, 李卿, 高婷, 付立叶, 王扬, 蒋涛, 姜又红. 树突状细胞分泌的exosomes体外诱导特异性CTL抗肾癌的初步研究[J]. 中国医科大学学报, 2010, 39(1): 4 .
[3] 刁延娜, 马兰兰, 孟凡彪, 李宏图, 庞希宁. 骨髓间充质干细胞移植促进大鼠损伤脊髓的功能恢复[J]. 中国医科大学学报, 2010, 39(1): 7 .
[4] 张依宁, 魏敏杰, 孙明军. 伊立替康抑制人结直肠癌细胞增殖和ATP敏感性钾通道的相关性研究[J]. 中国医科大学学报, 2010, 39(1): 10 .
[5] 赵宇, 谢鹏, 朱晓峰, 蔡志友. 大鼠神经干细胞中MAPKK/MEK-MAPK/ERK信号转导通路的实验研究[J]. 中国医科大学学报, 2010, 39(1): 14 .
[6] 夏蒲, 徐小燕, 贾宝萍, 王薇, 关一夫, 高野康雄, 郑华川. 胃黏膜特异表达JC病毒T抗原质粒构建及表达鉴定[J]. 中国医科大学学报, 2010, 39(1): 18 .
[7] 黄海能, 罗起胜, 赵邦, 谭源福, 邓元央, 黄华东, 符黄德, 李传玉. 兔脑创伤后早期血清β淀粉样前体蛋白动态变化的实验研究[J]. 中国医科大学学报, 2010, 39(1): 22 .
[8] 朱馥丽, 韩劲松, 姚颖, 王一婷, 张坤. 硅胶子宫托保守治疗对盆腔脏器脱垂患者症状和生活质量的影响[J]. 中国医科大学学报, 2010, 39(1): 51 .
[9] 孙桂莲, 江雅静, 姜琳, 王东颖, 杨志亮. 46例小儿周期性呕吐综合征的临床研究[J]. 中国医科大学学报, 2010, 39(1): 67 .
[10] 程敏. 细小钙化根管的临床治疗[J]. 中国医科大学学报, 2011, 40(10): 909 .

中国医科大学学报版权所有©2018

未经允许,严禁擅自转载本站图文资料

地址:中国 沈阳市沈北新区蒲河路77号 110122

辽ICP备05014850

JOURNAL OF CHINA MEDICAL UNIVERSITY

ADDRESS: NO.77 PUHE ROAD

SHENYANG NORTH NEW AREA, SHENYANG

LIAONING PROVINCE, P.R. CHINA