抗IgG和IgA-CCP抗体与MCV抗体在早期RA诊断中的对比研究

抗IgG和IgA-CCP抗体与MCV抗体在早期RA诊断中的对比研究

徐 宁

     摘要  研究目的：因为其敏感性修饰后抗波形蛋白抗体一直被认为其诊断敏感性优于抗环瓜氨酸多肽抗体，同时，在类风湿关节炎患者中抗环瓜氨酸肽抗体具有更好的诊断特异性。在本研究中我们评估了IgG 和 IgA型的 anti-CCP 以及anti-MCV作为诊断与预后标记在早期类风湿关节炎患者中的情况。

    研究方法：两大瑞典关节炎患者人群被检测：其中215例早期类风湿关节炎患者（病程小于12个月）来自瑞典TIRA—1人群，69例极早期关节炎患者（病程小于3个月）来自Kronoberg关节炎人群，其中22%已经被诊断为类风湿关节炎。抗环瓜氨酸抗体IgG型以及抗波形蛋白抗体应用试剂盒进行了检测分析，这些实验应用IgA亚型抗体检测进行了校正。这些结果显示与疾病病程，吸烟习惯以及共享抗原表位状态相关。

    研究结果：在TIRA人群中，抗波形蛋白抗体IgG亚型与抗环瓜氨酸抗体IgG亚型有93%的重叠率，尽管抗波形蛋白抗体IgG亚型有更高的诊断敏感性。其中抗波形蛋白抗体IgA亚型有24%的阳性率，抗环瓜氨酸抗体IgA亚型有29%的阳性率。在Kronoberg关节炎人群中有抗波形蛋白抗体IgG亚型有15%的阳性率，抗波形蛋白抗体IgA亚型有6%的阳性率，同时，抗环瓜氨酸抗体IgG亚型有10%的阳性率，抗环瓜氨酸抗体IgA亚型有3%的阳性率，揭示出抗环瓜氨酸抗体有更强的类风湿关节炎诊断特异性。根据以往文献报道，抗波形蛋白抗体IgA亚型与抗环瓜氨酸抗体IgA亚型均出现在高水平IgG亚型阳性血清中，而且都与更严重的侵袭性疾病发展过程相关。吸烟的患者，更容易出现环瓜氨酸抗体阳性，其中抗波形蛋白抗体IgA亚型的阳性率更为显著。

    研究结论：在早期类风湿关节炎患者中抗波形蛋白抗体IgG亚型与抗环瓜氨酸抗体IgG亚型的阳性发生情况大致重叠。其中抗波形蛋白抗体的阳性率更高，抗环瓜氨酸抗体具有更好的诊断特异性。抗波形蛋白抗体的阳性率可能与更加不利的疾病发展过程相关。尽管随时间推移疾病活动度加强，但是抗波形蛋白抗体IgA亚型与抗环瓜氨酸抗体IgA亚型未显示更高的诊断优势。

    附原文：Abstract  OBJECTIVE: Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis.METHODS: Two Swedish arthritis populations were examined: 215 patients with early RA (≤ 12 months' duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (≤ 3 months' duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. Results were related to disease course, smoking habits, and shared epitope status.RESULTS: In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive.CONCLUSION: The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.

     引自：A comparison between IgG- and IgA-class antibodies to cyclic citrullinated peptides and to modified citrullinated vimentin in early rheumatoid arthritis and very early arthritis. J Rheumatol. 2011 Jul;38(7):1265-72. Epub 2011 Apr 1.