Vossenaar Erik R, Smeets Tom J M, Kraan Maarten C, Raats Jos M, van Venrooij Walther J, Tak Paul P
Department of Biochemistry 161, Radboud University Nijmegen, NL-6500 HB Nijmegen, The Netherlands.
Arthritis Rheum. 2004 Nov;50(11):3485-94. doi: 10.1002/art.20584.
Antibodies directed toward citrullinated proteins (e.g., anti-cyclic citrullinated peptide antibodies) are highly specific for rheumatoid arthritis (RA) and are produced locally at the site of inflammation. Although the presence of citrullinated proteins in rheumatoid synovium has been described in the literature, it is uncertain whether their presence is specific for RA. The present study was undertaken to investigate this.
The local production of the anti-citrullinated protein antibodies was investigated by comparing the concentration of the antibodies (corrected for the total amount of IgG present) in paired samples of serum and synovial fluid from RA patients. The presence of citrullinated proteins in the synovial tissue was investigated by immunohistochemical analysis of synovial tissue from RA patients and from patients with other arthropathies, using a variety of specific antibodies to citrullinated proteins.
In RA patients, anti-citrullinated protein antibodies constituted a 1.4-fold higher proportion of IgG in synovial fluid compared with serum, which is indicative of a local production of the antibodies. Immunohistochemical staining of citrullinated proteins was observed in the lining layer, the sublining layer, and in extravascular fibrin deposits in inflamed synovial tissue from RA as well as non-RA patients.
The presence of citrullinated proteins in the inflamed synovium is not specific for RA, but rather, it may be an inflammation-associated phenomenon. The high specificity of the anti-citrullinated protein antibodies is, therefore, most likely the result of an abnormal humoral response to these proteins.
针对瓜氨酸化蛋白的抗体（如抗环瓜氨酸肽抗体）对类风湿关节炎（RA）具有高度特异性，且在炎症部位局部产生。尽管文献中已描述类风湿滑膜中存在瓜氨酸化蛋白，但其存在是否对RA具有特异性尚不确定。本研究旨在对此进行调查。
通过比较RA患者血清和滑液配对样本中抗体浓度（校正存在的IgG总量）来研究抗瓜氨酸化蛋白抗体的局部产生情况。使用多种针对瓜氨酸化蛋白的特异性抗体，通过对RA患者和其他关节病患者的滑膜组织进行免疫组织化学分析，来研究滑膜组织中瓜氨酸化蛋白的存在情况。
在RA患者中，与血清相比，滑液中抗瓜氨酸化蛋白抗体在IgG中所占比例高1.4倍，这表明抗体是局部产生的。在RA患者以及非RA患者的炎症滑膜组织的衬里层、衬里下层和血管外纤维蛋白沉积物中均观察到瓜氨酸化蛋白的免疫组织化学染色。
炎症滑膜中瓜氨酸化蛋白的存在并非RA所特有，相反，它可能是一种与炎症相关的现象。因此，抗瓜氨酸化蛋白抗体的高度特异性很可能是对这些蛋白异常体液反应的结果。
