The presence of citrullinated proteins is not specific for rheumatoid synovial tissue
The presence of citrullinated proteins is not specific for rheumatoid synovial tissue
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DOI：
10.1002/art.20584
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发表时间：
2004-11-01
影响因子：
--
通讯作者：
Tak, PP
中科院分区：
文献类型：
--
作者：
Vossenaar, ER;Smeets, TJM;Tak, PP
Objective.针对瓜氨酸化蛋白的抗体（例如，抗环瓜氨酸肽抗体）对类风湿性关节炎（RA）具有高度特异性，并且在炎症部位局部产生。虽然文献中已经描述了类风湿性滑膜中存在瓜氨酸化蛋白，但尚不确定它们的存在是否对RA具有特异性。本研究进行了调查。通过比较RA患者血清和滑液配对样本中的抗体浓度（针对存在的IgG总量进行校正），研究抗瓜氨酸化蛋白抗体的局部产生。通过免疫组化分析RA患者和其他关节病患者的滑膜组织，使用多种瓜氨酸化蛋白的特异性抗体，研究了滑膜组织中瓜氨酸化蛋白的存在。在RA患者中，与血清相比，抗瓜氨酸化蛋白抗体在滑液中占IgG的比例高1.4倍，这表明抗体的局部产生。瓜氨酸化蛋白的免疫组化染色可见于RA和非RA患者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。瓜氨酸化蛋白在炎症滑膜中的存在不是RA的特异性，而是一种炎症相关现象。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质的异常体液应答的结果。
Objective. 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.Methods. 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.Results. 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.Conclusion. 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.