Department of Rheumatology, Leiden University Medical Center, The Netherlands.
Ann Rheum Dis. 2012 Feb;71(2):268-74. doi: 10.1136/annrheumdis-2011-200421. Epub 2011 Oct 13.
Anticitrullinated protein antibodies (ACPA) are the most predictive factor for the development of rheumatoid arthritis (RA). Epitope spreading towards more citrullinated epitopes occurs before the onset of RA. Here, the authors investigated whether specific epitope recognition allows the identification of specific RA subgroups and whether it is associated with clinical features of RA.
The reactivity of 661 patients with RA from the Leiden Early Arthritis Clinic against several citrullinated antigens was determined by ELISA. Cluster analyses were performed to identify subgroups of patients on the basis of their ACPA recognition profile. The association of the specific reactivities with clinical characteristics was studied.
ACPA-positive patients displayed a heterogeneous ACPA recognition profile. After performing cluster analyses, no apparent clustering of patients was found, and on the basis of the reactivities analysed, 64 different subgroups could already be identified. The extent of epitope recognition was associated with anticyclic citrullinated peptide-2 levels. The recognition of specific citrullinated epitopes was not associated with baseline characteristics. Likewise, patients with an extended fine specificity repertoire did not display differences in baseline characteristics or joint damage after 7 years of follow-up using cyclic citrullinated peptide-2 levels as a proxy, compared to ACPA-positive patients recognising fewer peptides.
These data show that the ACPA response is highly diverse with respect to recognition of specific citrullinated epitopes. Furthermore, the authors' data indicate that clinical correlates in established ACPA-positive RA are independent from the specific (group of) citrullinated peptides recognised.
抗瓜氨酸化蛋白抗体（ACPA）是类风湿关节炎（RA）发展的最具预测性的因素。在 RA 发病前，就会出现针对更多瓜氨酸化表位的抗原表位扩展。作者在此研究了特定表位识别是否能够识别特定的 RA 亚组，以及是否与 RA 的临床特征相关。
通过 ELISA 测定来自莱顿早期关节炎诊所的 661 例 RA 患者对几种瓜氨酸化抗原的反应性。通过聚类分析，根据 ACPA 识别谱确定患者的亚组。研究了特定反应性与临床特征的相关性。
ACPA 阳性患者表现出 ACPA 识别谱的异质性。在进行聚类分析后，未发现明显的患者聚类，并且根据分析的反应性，已经可以识别出 64 个不同的亚组。表位识别的程度与环瓜氨酸肽-2 水平相关。特定瓜氨酸化表位的识别与基线特征无关。同样，与识别较少肽的 ACPA 阳性患者相比，使用环瓜氨酸肽-2 水平作为替代物，在 7 年的随访中，具有扩展精细特异性谱的患者在基线特征或关节损伤方面没有差异。
这些数据表明，针对特定瓜氨酸化表位的 ACPA 反应具有高度多样性。此外，作者的数据表明，在已确立的 ACPA 阳性 RA 中，临床相关性与所识别的特定（组）瓜氨酸化肽无关。
