类风湿关节炎新血清学指标研究与临床初步应用  

Study of new serum parameters in patients with rheumatoid arthritis and its preliminary application

作　　者：虞伟[1] 王金花[1] 白彩琴[1] 高佩芳[1] 房国祥[1] 张晶[1] 夏海萍[1] 李晓军[1] 武建国[1] 

机构地区：[1]南京军区南京总医院解放军临床检验医学研究所中心实验科,南京210002

出　　处：《临床检验杂志》2011年第1期2-6,共5页Chinese Journal of Clinical Laboratory Science

基　　金：国家自然科学基金项目(81071419);中国博士后科学基金特别资助项目(200801375)

摘　　要：目的建立并完善类风湿关节炎(RA)血清学实验诊断体系,寻找新的RA标志性自身抗体,探讨其在RA疾病发生、发展中的诊断价值。方法采用肽酰精氨酸脱亚氨基酶(PAD)分别对人纤维蛋白原(hFib)和牛Ⅱ型胶原(bCⅡ)瓜氨酸化(cit-rullination,Cit),以环瓜氨酸肽(CCP)作对照,并选择CⅡ短肽(CⅡ260-272),建立检测3种抗原自身抗体的ELISA法,进行临床标本检测及与其他实验室指标进行相关分析,评价其对RA的诊断价值。结果抗Cit-hFib和抗Cit-bCⅡ抗体在RA患者血清中的检出率分别为59.4%和56.3%,均显著高于其他疾病和健康对照组(P均<0.01)。诊断RA的敏感性和特异性均较抗hFib和抗bCⅡ抗体有明显提高。抗CⅡ短肽抗体对RA的诊断效能与抗CCP抗体接近,对RA的诊断敏感性分别为67.2%和68.8%;特异性分别为95.3%和97.8%;阳性预测值分别为76.8%和88.0%;阴性预测值分别为92.6%和93.1%;阳性似然比分别为14.3和31.3;阴性似然比分别为0.34和0.32;Youden指数分别为0.625和0.666。在13例早期RA患者中,抗CⅡ短肽抗体和抗CCP抗体阳性率均为76.9%。抗CCP抗体对RA诊断的ROC曲线下面积(AUC)值为0.946,抗CⅡ短肽抗体为0.924。联合应用抗CⅡ短肽与抗CCP抗体、或抗CⅡ短肽与RF,均可进一步提高对RA的有效诊断水平。相关分析和一致性检验结果显示,各自身抗体均与抗CCP抗体显著相关,仅有抗Cit-hFib抗体、抗Cit-bCⅡ抗体与抗CCP抗体检出结果表现出较好的同步性(0.4<Kappa<0.75),检出符合率分别为84.4%(54/64)和78.1%(50/64)。各自身抗体水平均与C反应蛋白(CRP)、血沉(ESR)呈高度正相关(P均<0.01),提示与RA疾病活动程度密切相关;抗CⅡ短肽抗体水平有随RA临床症状改善而明显下降趋势。结论瓜氨酸化蛋白及其自身抗体在RA疾病发生、发展过程中起重要作用。抗CⅡ短肽抗体及抗CCP、抗Cit-hFib和抗Cit-bCⅡ抗体均与RA疾病活动性密切相关,这些抗体可能发展成�Objective To establish and perfect the serological test system for diagnosis of rheumatoid arthritis（RA）,search for new autoantibody markers of RA,and explore the role and clinical significance of these parameters in occurrence and development of RA.Methods Human fibrinogen（hFib） and bovine type Ⅱ collagen（bCⅡ） were modified and citrullinated by peptidylarginine deiminase（PAD）,respectively.CⅡ peptide（CⅡ 260-272） and cyclic citrullinated peptide（CCP） were selected as immobilized antigens.The enzyme-linked immunosorbent assay（ELISA） for autoantibodies against Cit-hFib,Cit-bCⅡ,CⅡ peptide and CCP antigens were established.The positive rates of these autoantibodies in clinical patients and the relationship with other laboratory parameters were also analyzed.The diagnostic value of these autoantibodies was assessed in the patients with RA.Results The positive rates of anti-Cit-hFib and anti-Cit-bCⅡ antibody in the patients with RA were 59.4% and 56.3% respectively,and were significantly higher than those in the patients with other diseases and healthy controls（P0.01）.The sensitivity and specificity of these antibodies for RA diagnosis were significantly higher than those of anti-hFib and anti-bCⅡ antibody.The diagnostic value of anti-CⅡ peptide antibody was close to that of anti-CCP antibody.The diagnostic sensitivities of anti-CⅡ peptide and anti-CCP antibody for RA were of 67.2% and 68.8%,and the specificities were of 95.3% and 97.8%.The positive/negative predictive values were of 76.8%/88.0% and 92.6% /93.1% respectively.The positive/negative likelihood ratios were 14.3/31.3 and 0.34/0.32 respectively.Youden indexes were up to 0.625 and 0.666.In 13 patients with early stage of RA,the frequencies of both anti-CⅡ peptide and anti-CCP antibody were up to 76.9%.The area under the ROC curve of anti-CCP antibody was of 0.946,and anti-CⅡ peptide antibody was of 0.924.The combination of anti-CⅡ peptide and anti-CCP antibody or anti-CⅡ peptide and rheumatoid factor

关 键 词：类风湿关节炎 纤维蛋白原 Ⅱ型胶原 瓜氨酸化蛋白 自身抗体 免疫酶技术 

分 类 号：R446.6[医药卫生—诊断学] R593.22[医药卫生—临床医学]