Email Alert | RSS

北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (6): 1003-1007. doi: 10.19723/j.issn.1671-167X.2019.06.004

• 论著 • 上一篇    下一篇

抗氨基甲酰化蛋白抗体在类风湿关节炎合并肺间质病变早期诊断中的价值

竺红1,△(),赵丽娟2,周艳1,陈瑶2   

  1. 1. 宁夏医科大学总医院风湿免疫科,宁夏银川 750004
    2. 宁夏医科大学临床医学院,宁夏银川 750004
  • 收稿日期:2019-08-26 出版日期:2019-12-18 发布日期:2019-12-19
  • 通讯作者: 竺红 E-mail:nxzhuh@126.com
  • 基金资助:
    宁夏自然科学基金(NZl6160)

Significance of anti-carbamylated protein antibodies in patients with rheumatoid arthritis-associated intersitial lung disease

Hong ZHU1,△(),Li-juan ZHAO2,Yan ZHOU1,Yao CHEN2   

  1. 1. Department of Rheumatology, General Hospital of Ningxia Medical University, Yinchuan 750004, China
    2. Department of Clinical Medical College, Ningxia Medical University, Yinchuan, 750004, China
  • Received:2019-08-26 Online:2019-12-18 Published:2019-12-19
  • Contact: Hong ZHU E-mail:nxzhuh@126.com
  • Supported by:
    Supported by Ningxia Natural Science Foundation(NZl6160)

RICH HTML

 19   

PDF (PC)

296

摘要：

目的 探讨抗氨基甲酰化蛋白(carbamylated protein, CarP)抗体在类风湿关节炎(rheumatoid arthritis,RA)合并肺间质病变 (interstitial lung disease,ILD)早期诊断中的价值。方法 选择2017年12月至2019年6月在宁夏医科大学总医院风湿免疫科住院确诊为RA的患者,收集病例资料及血清标本,依据胸部CT检查结果分为RA-ILD组及单纯RA组,采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)法测定各组血清中抗CarP抗体水平,分析其与RA-ILD的发生及其他实验室指标的相关性。组间计量资料比较采用两独立样本t检验或Mann-Whitney U检验;组间计数资料比较采用卡方检验;采用绘制受试者工作曲线(ROC曲线)确定抗CarP抗体对诊断RA-ILD最佳截断值并分析其诊断效能,相关性分析采用Spearman相关分析。结果 RA-ILD组抗CarP抗体水平为21.14(12.29,29.75), 明显高于单纯RA组的11.00(6.66,19.05),差异有统计学意义(P<0.05)。RA-ILD组抗CarP抗体阳性率(53%)高于单纯RA组(16%),差异有统计学意义(P<0.05);两组间类风湿因子(rheumatoid factor,RF)及抗环瓜氨酸肽(cyclic citrullinated peptide,CCP)抗体水平差异无统计学意义(P>0.05)。RA-ILD组年龄及疾病活动指数(disease activity score 28,DAS28)显著高于单纯RA组,差异有统计学意义(P<0.05)。RA-ILD组男性和吸烟比例高于单纯RA组,但差异无统计学意义(P>0.05)。通过绘制R0C曲线显示抗CarP抗体对RA-ILD诊断的最佳截断值为20.56 U/mL,灵敏度为53.50%,特异度为84.20%,曲线下面积为0.76 ;Spearman相关性分析示RF、年龄与抗CarP抗体呈正相关(r=0.172,P=0.043;r=0.200,P=0.006);抗CarP抗体水平与 DAS28 评分、红细胞沉降率(erythrocyte sedimentation rate,ESR)、C-反应蛋白(C-reactive protein, CRP)、抗CCP抗体、关节肿胀数和关节压痛数均无相关性(P>0.05)。结论 RA-ILD患者中血清抗CarP抗体浓度高于单纯RA患者,提示抗CarP抗体在RA-ILD发生发展中可能具有一定作用。

关键词: 类风湿关节炎, 抗氨基甲酰化蛋白抗体, 肺间质病变

Abstract:

Objective: To evaluate the value of anti-carbamylated protein (CarP) antibody in the diagnosis of rheumatoid arthritis-associated intersitial lung diseas (RA-ILD).Methods: Clinical and laboratory data and serum samples of patients with RA between December 2017 and June 2019 in Department of Rheumatology, General Hospital of Ningxia Medical University were collected. The patients were subclassified as RA-ILD and RA-without ILD based on computed tomography scans of the chest, Enzyme 1inked immunosorbent assay (ELISA) was used to assess anti-CarP antibody in the serum of each group. The occurrence of ILD and other laboratory indexes were analyzed. Comparison of measurement data between the 2 groups was performed by two independent sample t-test or Mann-Whitney U nonparametric test, while the count data were compared by Chi square test; Receiver operating characteristic curve (ROC) was drawn to determine the cut-off value of anti-CarP antibody to RA-ILD diagnosis and to analyze its diagnostic efficacy.Results: The anti-CarP antibody level in the RA-ILD group was 21.14 (12.29, 29.75), which was significantly higher than that in the RA-without ILD group 11.6 (6.66, 19.05) (P=0.000). The difference was statistically significant (P<0.05). The positive rate of anti-CarP antibody in RA-ILD group (53%) was significantly higher than that in RA-without ILD group (16%) (P<0.05); There was no significant differences in the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) between the two groups (P>0.05). The age and disease activity score (DAS28) in the RA-ILD group were significantly higher than those in the RA-withhout ILD group (P<0.05). The proportion of men and smoking in the RA-ILD group was higher than that in the RA-without ILD group, but the difference was not statistically significant. The ROC curve showed that the anti-CarP antibody had a cut off value of 20.56 U/mL, with the sensitivity of 53.50%, and specificity of 84.20%, the area under the ROC curve were 0.76. Spearman correlation analysis showed that rheumatoid factor (RF) and age were positively correlated with anti-CarP antibody (r=0.172, P=0.043; r=0.200, P=0.006). Anti-CarP antibody level was not associated with the DAS28 score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-CCP antibody, swollen joint count, and tender joint count (P>0.05).Conclusion: The anti-CarP antibody level in RA-ILD patients is higher than that in RA-without ILD, suggesting that anti-CarP antibody may have a role in the development of RA-ILD.

Key words: Rheumatoid arthritis, Anti-carbamylated protein antibody, Intersitial lung disease

中图分类号: 

  • R593.22

表1

两组患者一般资料比较"

Group Total cases Age/years, x?±s Course of disease, M(P25,P75) DAS28, x?±s Gender Smoking
Male % Cases %
RA-ILD 129 60±10 6 (2,12) 5.7±1.2 29 22 14 11
RA-without ILD 57 48±13 6 (2,10) 5.0±1.3 7 12 4 7
t/U/χ2 6.913 3 585 3.948 2.635 0.665
P 0.000 0.786 0.000 0.105 0.415

表2

两组血清抗CarP抗体、RF及抗CCP抗体水平比较[M(P25,P75)]"

Group Cases Anti-CarP/(U/mL) RF/(U/mL) Anti-CCP/(U/mL)
RA-ILD 129 21.14(12.29,29.75) 102.00(12.50,256.50) 71.35(8.95,200)
RA-without ILD 57 11.00(6.66,19.05) 70.70(21.13,223.75) 68.35(7.00,139.80)
U 1 803 3 668 3 273
P 0 0.98 0.346

图1

抗CarP抗体用于RA-ILD诊断的ROC曲线"

表3

抗CarP抗体与RA病情活动相关性分析"

Items Anti-CarP
r P
DAS28 0.029 0.691
ESR 0.05 0.941
CRP 0.35 0.632
RF 0.172 0.043
Anti-CCP -0.039 0.598
Age 0.2 0.006
Swollen joint count -0.084 0.254
Tender joint count 0.06 0.417
[1] Ellman P, Ball RE . Rheumatoid disease with joint and pulmonary manifestations[J]. Br Med J, 1984,2(4583):816-820.
[2] Bongartz T, Nannini C, Medina-Velasquez YF , et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: apopulation-based study[J]. Arthritis Rheum, 2010,62(6):1583-1591.
[3] 钟岩 . 类风湿关节炎合并间质性肺疾病的临床特点和危险因素分析[J]. 中国保健营养, 2017,27(18):119-120.
[4] Šenolt L, Grassi W . Laboratory biomarkers or imaging in the diagnostics of rheumatoid arthritis[J]. BMC medicine, 2014,12(3):49-54.
[5] 黄清水, 万腊根, 罗忠勤 , 等. 抗环瓜氨酸肽抗体对类风湿关节炎诊断价值的荟萃分析[J]. 中华医学杂志, 2006,86(31):2182-2187.
[6] Shi J, van de Stadt LA, Levarht EW , et al. Anti-carbamylated protein antibodies are present in arthralgia patients and predict the development of rheumatoid arthritis[J]. Arthritis Rheum, 2013,65(4):911-915.
[7] Scinocca M, Bell DA, Racape M , et al. Antihomocitrullinated fibrinogen antibodies are specific to rheumatoid arthritis and frequently bind citrullinated proteins/peptides[J]. J Rheumatol, 2014,41(2):270-279.
[8] 竺红, 罗云霞, 杨亚珊 . 抗氨基甲酰化蛋白抗体在类风湿关节炎诊断价值中的评价. 中华风湿病学杂志, 2017,21(6):387-391
[9] Mohd NN, Mohd Shahrir MS, Shahid MS , et al. Clinical and high resolution computed tomography characteristics of patients with rheumatoid arthritis lung disease[J]. Int J Rheum Dis, 2009,12(2):136-144.
[10] Zou YQ, Li YS, Ding XN , et al. The clinical significance of HRCT in evaluation of patients with rheumatoid arthritis-associated interstitial lung disease: a report from China[J]. Rheumatol Int, 2012,32(3):669-673.
[11] Solomon JJ, Brown KK . Rheumatoid arthritis-associated interstital lung disease[J]. Open Access Rheumotal Res Rev, 2012,1(4):21-31.
[12] Assayag D, Lubin M, Lee JS , et al. Predictors of mortality in rheumatoid arthritis-related interstitial lung disease[J]. Respirology, 2014,19(4):493-500.
[13] Dawson JK, Fewins HE, Desmond J , et al. Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests[J]. Thorax, 2001,56(8):622-627.
[14] Tanaka N, Kim JS, Newell JD , et al. Rheumatoid arthritis-related interstitial lung disease: CT findings[J]. Radiology, 2004,232(1):81-91.
[15] Demoruelle MK, Solomon JJ, Fischer A , et al. The lung may play a role in the pathogenesis of rheumatoid arthritis[J]. Int J Clin Rheumtol, 2014,9(3):295-309.
[16] Reynisdottir G, Karimi R, Joshua V , et al. Structural changes and antibody enrichment in the lungs are early features of anti-citrullinated protein antibody-positive rheumatoid arthritis[J]. Arthritis Rheum, 2014,66(1):31-39.
[17] Kelly CA, Saravanan V, Nisar M , et al. Rheumatoid anhritis-related interstitial lung disease:associations,prognostic factors and physiological and radiological characteristics: a large multicentre UK study[J]. Rheumatology(0xford), 2014,53(9):1676-1682.
[18] Basnakian AG, Shah SV, Ok E , et al. Carbamylated LDL[J]. Adv Clin Chem, 2010,51:25-52.
[19] Shi J, Knevle 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.
[20] Li L, Deng C, Chen S , et al. Meta-analysis:diagnostic accuracy of anti-carbamylated protein antibody for rheumatoid arthritis[J]. PLoS One, 2016,11(7):e0159000.
[21] Ajeganova S, van Steenbergen HW, Verheul MK , et al. The association between anti-carbamylated prolein(anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor[J]. Ann Rheum Dis, 2017,76(1):112-118.
[22] Brink M, Verheul MK, Rnnelid 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(1):523-533.
[23] 郑晓, 王玉梅, 刘秀梅 . 抗氨甲酰化蛋白抗体对类风湿关节炎的诊断价值[J]. 中华临床医师杂志: 电子版, 2017,11(4):570-573.
[24] Restrepo JF, del Rincon I, Battafarano DF , et al. Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis[J]. Clin Rheumatol, 2015,34(9):1529-1536.
[25] Sparks JA, He X, Huang J , et al. Rheumatoid arthritis disease activity predicting incident clinically apparent rheumatoid arthritis-associated interstitial lung disease: a prospective cohort study[J]. Arthritis Rheum, 2019,71(9):1472-1482.
[26] Othman MA, Ghazal WSW, Hamid WZWA , et al. Anti-carbamylated protein antibodies in rheumatoid arthritis patients and their association with rheumatoid factor[J]. Saudi Med J, 2017,38(9):934-941.
[1] 张璐,胡小红,陈澄,蔡月明,王庆文,赵金霞. 类风湿关节炎初治患者颈椎失稳情况及临床特征[J]. 北京大学学报（医学版）, 2021, 53(6): 1049-1054.
[2] 罗靓,霍文岗,张钦,李春. 类风湿关节炎合并角膜溃疡的临床特点和相关因素分析[J]. 北京大学学报（医学版）, 2021, 53(6): 1032-1036.
[3] 钟华,徐丽玲,白明欣,苏茵. 类风湿关节炎患者趋化因子CXCL9和CXCL10在骨侵蚀中的作用[J]. 北京大学学报（医学版）, 2021, 53(6): 1026-1031.
[4] 娄雪,廖莉,李兴珺,王楠,刘爽,崔若玫,徐健. 类风湿关节炎患者外周血TWEAK基因启动子区甲基化状态及其表达[J]. 北京大学学报（医学版）, 2021, 53(6): 1020-1025.
[5] 曹迪,王燕,王柳青,孙晓麟,黄妃,孟洋,任丽丽,张学武. 血浆Dickkopf-1在类风湿关节炎患者中的表达及其与外周血T细胞亚群的相关性[J]. 北京大学学报（医学版）, 2021, 53(2): 255-260.
[6] 赵凯,常志芳,王志华,庞春艳,王永福. 基因沉默肽基精氨酸脱亚胺酶4的表达对胶原诱导关节炎小鼠肺间质病变的影响[J]. 北京大学学报（医学版）, 2021, 53(2): 235-239.
[7] 钟剑球,曾沛英,王庆文. 类风湿关节炎合并淋巴水肿2例及文献回顾[J]. 北京大学学报（医学版）, 2020, 52(6): 1157-1161.
[8] 唐果,龙丽,韩雅欣,彭清,刘佳君,尚华. 类风湿关节炎合并结核感染的临床特点及相关因素[J]. 北京大学学报（医学版）, 2020, 52(6): 1029-1033.
[9] 张警丰,叶修玲,段萌,周小利,姚中强,赵金霞. 抗核抗体阳性类风湿关节炎的临床和实验室检查特点[J]. 北京大学学报（医学版）, 2020, 52(6): 1023-1028.
[10] 张璐,胡小红,王庆文,蔡月明,赵金霞,刘湘源. 类风湿关节炎合并颈椎失稳的人群分布及临床特征[J]. 北京大学学报（医学版）, 2020, 52(6): 1034-1039.
[11] 陈家丽,金月波,王一帆,张晓盈,李静,姚海红,何菁,李春. 老年发病类风湿关节炎的临床特征及其心血管疾病危险因素分析:一项大样本横断面临床研究[J]. 北京大学学报（医学版）, 2020, 52(6): 1040-1047.
[12] 彭嘉婧,刘田. 类风湿关节炎合并色素沉着绒毛结节性滑膜炎1例及文献回顾[J]. 北京大学学报（医学版）, 2020, 52(6): 1135-1139.
[13] 罗采南,李正芳,武丽君,陈海娟,杨春梅,徐文晖,刘小玲,唐薇,乔平,热娜·白合提亚. 类风湿关节炎不同分类标准的多中心临床比较[J]. 北京大学学报（医学版）, 2020, 52(5): 897-901.
[14] 张晓英,靳家扬,何菁,甘雨舟,陈家丽,赵晓珍,刘佳佳,尤旭杰,李雪,郭建萍,李小峰,李静,李茹,栗占国. 类风湿关节炎患者风湿病家族史特征及临床意义[J]. 北京大学学报（医学版）, 2019, 51(3): 439-444.
[15] 王莉,高超,朱笛,陈立红. 功能锻炼对类风湿关节炎患者效果评价的meta分析[J]. 北京大学学报（医学版）, 2018, 50(6): 991-997.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 张三. 中文标题测试[J]. 北京大学学报（医学版）, 2010, 42(1): 1 -10 .
[2] 赵磊, 王天龙 . 右心室舒张末期容量监测用于肝移植术中容量管理的临床研究[J]. 北京大学学报（医学版）, 2009, 41(2): 188 -191 .
[3] 万有, , 韩济生, John E. Pintar. 孤啡肽基因敲除小鼠电针镇痛作用增强[J]. 北京大学学报（医学版）, 2009, 41(3): 376 -379 .
[4] 张燕, 韩志慧, 钟延丰, 王盛兰, 李玲玲, 郑丹枫. 骨骼肌活组织检查病理诊断技术的改进及应用[J]. 北京大学学报（医学版）, 2009, 41(4): 459 -462 .
[5] 赵奇, 薛世华, 刘志勇, 吴凌云. 同向施压测定自酸蚀与全酸蚀粘接系统粘接强度[J]. 北京大学学报（医学版）, 2010, 42(1): 82 -84 .
[6] 林红, 王玉凤, 吴野平. 学校生活技能教育对小学三年级学生行为问题影响的对照研究[J]. 北京大学学报（医学版）, 2007, 39(3): 319 -322 .
[7] 丰雷, 程嘉, 王玉凤. 注意缺陷多动障碍儿童的运动协调功能[J]. 北京大学学报（医学版）, 2007, 39(3): 333 -336 .
[8] 李岳玲, 钱秋瑾, 王玉凤. 儿童注意缺陷多动障碍成人期预后及其预测因素[J]. 北京大学学报（医学版）, 2007, 39(3): 337 -340 .
[9] . 书讯[J]. 北京大学学报（医学版）, 2007, 39(3): 225 -328 .
[10] 牟向东, 王广发, 刁小莉, 阙呈立. 肺黏膜相关淋巴组织型边缘区B细胞淋巴瘤一例[J]. 北京大学学报（医学版）, 2007, 39(4): 346 -350 .
ISSN 1671-167X
CN 11-4691/R
主管单位：中华人民共和国教育部
主办单位：北京大学
地址： 北京市海淀区学院路38号 北京大学医学部 《北京大学学报（医学版）》
邮编：100191
电话：010-82801551
Email： xbbjb2@bjmu.edu.cn

《北京大学学报（医学版）》
微信公众号
版权所有 © 2018 《北京大学学报（医学版）》编辑部