The autoantibody response to cyclic citrullinated collagen type II peptides in rheumatoid arthritis
The autoantibody response to cyclic citrullinated collagen type II peptides in rheumatoid arthritis
复制标题
类风湿关节炎中环瓜氨酸胶原 II 型肽的自身抗体反应
DOI：
10.1093/rheumatology/kez073
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发表时间：
2019-09-01
期刊：
影响因子：
5.5
通讯作者：
Holmdahl, Rikard
中科院分区：
文献类型：
--
作者：
Liang, Bibo;Ge, Changrong;Holmdahl, Rikard
目标。抗瓜氨酸肽抗体 (ACPA) 的检测是 RA 的血清学标志。与 II 型胶原 (CII) 发生反应的自身抗体存在于 RA 血清和滑液中，具有潜在致病性。在这里，我们调查了中国 RA 队列中对源自 CII 的特定瓜氨酸环肽的自身抗体反应的普遍性和特异性。方法。使用基于微珠的多重检测，我们检查了 415 名 RA 患者以及 304 名 OA 患者中是否存在与 54 个环状 17 聚体瓜氨酸 CII 肽（涵盖 CII 中的所有瓜氨酸表位）以及相应的未修饰肽结合的自身抗体。此外，还在 203 名健康个体中检查了对一组选定的 10 种环瓜氨酸肽的自身抗体反应。结果。与 OA 患者或健康个体相比，RA 患者对环状瓜氨酸 CII 肽的自身抗体反应较高，而对环状未修饰 CII 肽的抗体反应很少或可忽略不计。有趣的是，几个新的瓜氨酸化 CII 表位被鉴定出来。这些新的瓜氨酸化 CII 表位的抗体不仅表现出大量重叠的反应性，而且还具有独特的特异性。结论。我们发现，在中国 RA 队列中，患者血清中抗环瓜氨酸 CII 自身抗体的患病率很高。本研究揭示了针对新型瓜氨酸 CII 表位的异质结合模式，这可能有助于将 RA 患者分为不同的亚组。
Objectives. The detection of anti-citrullinated peptide antibodies (ACPAs) is a serological hallmark of RA. Autoantibodies reactive with collagen type II (CII) are present in RA sera and synovial fluid and are potentially pathogenic. Here, we investigate the prevalence and specificity of the autoantibody responses to defined citrullinated cyclic peptides derived from CII in a China RA cohort.Methods. Using bead-based multiplex assay, we examined the presence of autoantibodies binding to 54 cyclic 17-mer citrullinated CII peptides, encompassing all citrullinate epitopes in CII, and the corresponding unmodified peptides in 415 RA patients, in addition to 304 patients with OA. Furthermore, the autoantibody responses to a selected set of 10 cyclic citrullinated peptides were also examined in 203 healthy individuals.Results. Autoantibody responses to cyclic citrullinated CII peptides were higher in RA patients as compared with OA patients or healthy individuals, whereas little or negligible antibody responses to cyclic unmodified CII peptides were observed. Interestingly, several novel citrullinated CII epitopes were identified. Antibodies to these novel citrullinated CII epitopes showed not only substantial overlapping reactivities but also had unique specificities.Conclusion. We found a high prevalence of autoantibodies against cyclic citrullinated CII in the sera of patients in a China RA cohort. The present study revealed heterogeneous binding patterns against novel citrullinated CII epitopes, which may help to stratify RA patients into different subgroups.