不同类型自身抗体对类风湿关节炎骨破坏程度的影响

Abstract

目的：探讨不同类型自身抗体及其他流行病学因素对类风湿关节炎( rheumatoid ar-thritis,RA)骨破坏严重程度的影响,以期发现RA骨破坏的独立危险因素。方法随机选取445例RA患者作为研究对象,收集患者流行病学资料,采用ELISA方法检测血清中类风湿因子( rheumatoid factor,RF)、抗环瓜氨酸肽抗体( anti-cyclic citrullinated peptide antibody,抗CCP抗体)和抗瓜氨酸化α烯醇化酶多肽1抗体[anti-citrullinated alpha-enolase peptide 1(CEP-1) antibody,抗CEP-1抗体]三种自身抗体的水平；采用修订版Sharp评分法( Sharp/van der Heijde score)对患者双手X线正位平片进行关节影像学评分。采用Mann-Whitney U检验分析两组间Sharp评分的差异；采用协方差分析法排除病程因素对组间Sharp评分比较的影响；采用单因素或多因素线性回归分析法评估导致关节影像学改变的可能危险因素及独立危险因素。结果单因素回归分析提示, RA患者的性别(女性,β=0.100, P=0.035)、病程(β=0.498, P=3.26×10-29)、RF(β=0.096, P=0.042)、抗CCP抗体(β=0.202, P=1.74×10-5)、抗CEP-1抗体(β=0.148, P=0.017)以及抗CCP和抗CEP-1抗体联合检测阳性(β=0.157, P=1.42×10-3)为 RA 患者关节破坏的潜在危险因素。而患者发病年龄晚(β=-0.312, P=1.60×10-11)及吸烟史(β=-0.121, P=0.018)可能为RA患者骨破坏的保护因素。进一步多因素回归分析表明,患者的病程和抗 CCP 抗体为其发生骨破坏的独立危险因素(病程：P=2.24×10-15,抗CCP抗体：P=0.012)。抗CCP抗体对RA骨破坏的影响主要发生在病程的中期(P=0.014)和晚期(P=0.023)。结论 RA患者的性别(女性)、病程、RF、抗CCP抗体和抗CEP-1抗体均为RA骨破坏的可能危险因素；抗瓜氨酸化抗体对RA骨破坏的作用主要发生在病程的中晚期；RA患者发病年龄越早,其骨破坏程度亦越严重。病程和抗CCP抗体为RA骨破坏的独立危险因素。

Objective To investigate any potential and independent demographic and serologic risk factors contributing to bone destruction in patients with rheumatoid arthritis ( RA) . Methods A total of 445 patients with RA were recruited in this study. Three autoantibodies including rheumatoid factor ( RF) , anti-cyclic citrullinated peptide antibody ( anti-CCP antibody) and anti-citrullinated alpha-enolase peptide 1 antibody ( anti-CEP-1 antibody) were quantified by using specific ELISA kits. The hand radiographs of all subjects were graded by using the modified Sharp/van der Heijde score ( Sharp score) . The potential and in-dependent risk factors were assessed by using univariate linear regression analyses and the stepwise multiple regression analysis, respectively. Results Based upon the univariate regression analyses, 7 covariates were identified as the potential risk factors for bone destruction in patients with RA, which were female (β=0. 100, P=0. 035), longer disease duration (β=0. 498, P=3. 26×10-29), RF (β=0. 096, P=0. 042), younger age at onset (β=-0. 312, P=1. 60 × 10-11 ), anti-CCP antibody positive (β=0. 202, P=1.74×10-5), anti-CEP-1 antibody positive (β=0.148, P=0.017) and positive for either anti-CCP or anti-CEP-1 antibodies (β=0. 157, P=1. 42×10-3). However, smoking (β=-0. 121, P=0. 018) were identi-fied as the potential protective factors. The multiple regression analysis indicated that the longer disease du-ration (P=2. 24×10-15) and anti-CCP antibody positive (P=0. 012) were independent risk factors for bone destruction. Conclusion Female, longer disease duration, younger age at onset, RF, anti-CCP and anti-CEP-1antibodies are potential risk factors for bone damage in patients with RA. Moreover, longer disease du-ration and anti-CCP antibody are two independent risk factors contributing to bone destruction in RA.