Low-avidity anticitrullinated protein antibodies (ACPA) are associated with a higher rate of joint destruction in rheumatoid arthritis
Low-avidity anticitrullinated protein antibodies (ACPA) are associated with a higher rate of joint destruction in rheumatoid arthritis
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DOI：
10.1136/annrheumdis-2012-202615
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发表时间：
2014-01-01
影响因子：
27.4
通讯作者：
Trouw, L. A.
中科院分区：
文献类型：
--
作者：
Suwannalai, Parawee;Britsemmer, Karin;Trouw, L. A.
目的抗纤氨酸化蛋白抗体（ACPA）是类风湿性关节炎（RA）的特异性抗体，与疾病的发病机制有关。以前我们已经表明，与针对召回抗原的抗体相比，ACPA显示出相当低的贪婪度。尽管如此，不同患者对acpa的渴望度确实有所不同。由于抗体介导的效应受到抗体亲和度的影响，我们现在研究了acpa亲和度与生物活性和临床结果的关系。方法：我们在两个荷兰早期ra队列中测定了ACPA的发生率，并将其与关节损伤的严重程度相关联，分别包含199例和132例患者。研究了低、高亲和度ACPA效应器功能的差异。结果不同患者间acpa贪婪度差异较大。这使得分析贪婪和严重程度之间的关系成为可能。低密度ACPA的存在与较高的关节破坏率有关。这一发现在一个独立的队列中得到了重复。对低亲和度ACPA与高亲和度ACPA特性的分析表明，低亲和度ACPA结合新瓜氨酸抗原的能力受到的阻碍较小。虽然在通过Fc-受体激活细胞方面没有观察到差异，但低剂量ACPA在激活补体系统方面更有效。结论低密度ACPA患者有较高的关节破坏率。低亲和力ACPA能及时与更多瓜氨酸化抗原相互作用，表明低亲和力ACPA具有更强的补体激活能力。这些数据表明（低）贪婪影响ACPA的生物活性，并与较差的放射预后相关。
Objectives Anticitrullinated protein antibodies (ACPA) are specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Previously we have shown that ACPA display a considerably lower avidity as compared with antibodies against recall antigens. Nonetheless, ACPA-avidity did vary between patients. As antibody mediated effects are influenced by antibody-avidity, we now investigated ACPA-avidity in relation to biological activity and clinical outcome.Methods We determined the avidity of ACPA and related this with severity of joint damage in two Dutch early-RA cohorts containing 199 and 132 patients respectively. Differences in effector functions of low- and high-avidity ACPA were studied.Results Extensive variation in ACPA-avidity between patients was observed. This allowed the analysis of the relationship between avidity and severity. The presence of low-avidity ACPA is associated with a higher rate of joint destruction. This finding was replicated in an independent cohort. Analysis of the properties of low-versus high-avidity ACPA revealed that low-avidity ACPA are less hampered in their ability to bind new' citrullinated antigens. Although no differences could be observed regarding cellular activation via Fc- receptors, low-avidity ACPA were more potent in activating the complement system.Conclusions Patients with low-avidity ACPA display a higher rate of joint destruction. Low-avidity ACPA display a higher potency to interact with more citrullinated antigens in time and show that low-avidity ACPA are more potent in complement activation. These data indicate that (low) avidity impacts on the biological activity of ACPA and associates with a worse radiological outcome.