目的:类风湿关节炎(rheumatoid arthritis,RA)患者血清中存在高滴度的特异性针对瓜氨酸化的人乳头状瘤病毒(human papilloma virus,HPV)47型E2蛋白的345-362多肽(human papilloma virus peptide,HPVP)抗原的抗体,探讨该抗体在早期RA临床诊断中的意义。方法:以HPVP及瓜氨酸化HPVP为抗原,酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测101例病程小于1年的早期RA(early RA,E-RA)患者,149例其他结缔组织病患者以及40名正常对照血清中相关抗体的水平。并与RA患者临床相关资料和实验室指标进行统计学分析。结果:(1)E-RA患者组血清中IgG、IgM型抗瓜氨酸化HPVP抗体的阳性率(分别为62.4%和66.3%)均高于其他对照组,差异有统计学意义(P〈0.01),而E-RA患者组及其他对照组血清的抗HPVP抗体阳性率差异无统计学意义;(2)抗瓜氨酸化HPVP的IgG型和IgM型抗体在E-RA诊断中的敏感性分别为62.4%和66.3%,特异性分别为89.4%和86.6%;(3)抗瓜氨酸化HPVP的IgG型和IgM型抗体在IgM-RF阴性患者中的阳性率分别是59.4%和71.9%,在抗环瓜氨酸肽(anticyclic citrullinated peptide,anti-CCP)抗体阴性的患者中阳性率分别为39.4%和51.5%,在IgM型类风湿因子(IgM-rheuwatord factor,IgM-RF)、抗角蛋白抗体(anti-keratin antibody,AKA)、抗核周因子(antiperinuclear factor,APF)三者皆阴性的患者中阳性率分别为54.5%和72.7%;(4)与E-RA临床及实验室指标比较显示,抗瓜氨酸化HPVP抗体的阳性组较阴性组疾病活动度DAS28高[IgG(6.3±1.0)vs.(5.6±0.9),P=0.002;IgM(6.2±1.1)vs.(5.6±0.8),P=0.008]、X线Ⅲ期以上改变比例高(IgG 56.1%vs.21.2%,P=0.001;IgM 50.9%vs.29.4%,P=0.036)、抗CCP抗体阳性率高(IgG 96.8%vs.55.3%,P=0.001;IgM 89.6%vs.64.7%,P=0.023)。另外,抗瓜氨酸化HPVP抗体阳性组ESR水平高于阴性组[IgG(70.3±32.4)vs.(51.9±27.8),P=0.004;IgM(67.4±31.5)vs.(53.8±27.7),P=0.03
Objective: To investigate the prevalence and the diagnostic values of antibodies to the cit- rullinated HPVP in early-stage rheumatoid arthritis. Methods: Antibodies against HPVP and citrullinated HPVP were detected by ELISA in the sera of 101 patients with early-stage RA, 149 patients with other rheumatic diseases and 40 healthy controls. The prevalence and diagnostic values of these antibodies for early-stage RA were analyzed by statistical software. Results: ( 1 ) The prevalence of IgG, IgM antibodies to citrullinated HPVP in early-stage RA were significantly higher than that in the patients with other rheumatic diseases as well as in the healthy individuals. (2) The diagnostic sensitivity of IgG and IgM citrulli- nated HPVP antibodies in early-stage RA were 62.4% and 66.3% respectively and the specificity value of the two antibody isotypes were 88.7% and 89.6% ,similar to that of the anti-CCP antibody. (3)The positivity rates of IgG and IgM antibodies against citrullinated HPVP were 59.4% and 71.9% in IgM-RF negative early-stage RA patients, and 39.4% and 51.5% in anti-CCP antibody negative early-stage RA patients. (4) TheDAS28 score [ IgG (6.3_+1.0) vs. (5.6+0.9), P=0.002; IgM (6.2±1.1) vs. (5.6±0.8), P=0.008] , X-ray stages (IgG 56. 1% vs. 21.2%, P=0.001;IgM 50.9% vs. 29.4%, P=0.036),anti-CCP antibodies(IgG 96. 8% vs. 55. 3%, P =0.001; IgM 89.6% vs. 64.7%, P = 0. 023 ) in citrullinated HPVPP positive patients were higher than those of citrullinated HPVP negative patients. Additionally, the levels of ESR [ IgG(70.3 ± 32.4)vs. (51.9 ± 27.8 ), P = 0. 004 ; IgM (67.4 ± 31.5 ) vs. (53.8 ± 27.7), P = 0. 035 ] in eitrullinated HPVP positive patients were higher than those of negative patients ( P 〈 0.05 ). Conclusion: IgG and IgM antibodies to citmllinated HPVP are highly sensitive and specific novel biomarkers for early-stage RA diagnosis, and are related to disease activity and joint damage.