抗环瓜氨酸肽抗体被证实早在类风湿关节炎（RA）首发症状出现前数年即可出现。来自瑞典于默奥大学的Mikael Brink等人进行了一项研究，该研究的目的是在RA首发症状出现前分析10种抗环瓜氨酸肽抗体反应性，研究结果在线发布在2013年4月的ARTHRITIS & RHEUMATISM（关节炎与风湿病）上。研究者发现，针对环瓜氨酸肽的免疫反应开始时受到抑制，但是，随着时间进展逐渐诱导出更严重的特异反应；同时，距离RA首发症状出现时间越近，抗体水平越高，特别是抗CEP-1、Fibβ36-52和中间丝相关蛋白抗体。

这是一项由瑞典北部医学生物资料库发起的病例对照研究。该研究共纳入409位研究对象，其中386位受试者在RA首发症状出现之前（pre-患者）捐献了717个全血标本，其距离RA发病的平均时间是7.4年。该研究还招募了共1,305位人群基础的对照者。采用微点阵方法对10种抗环瓜氨酸肽抗体进行分析：纤维蛋白原α573（Fibα573）、Fibα591 、Fibβ36-52、ibβ72，Fib 74、α-烯醇酶（环瓜氨酸α-烯醇酶肽1[CEP-1] ）、三倍螺旋型Ⅱ胶原肽C1（citC1Ⅲ）、中间丝相关蛋白、波形蛋白2-17（Vim2-17）和Vim60-75。

研究结果如下：pre-患者的抗Fibβ36-52、Fibβ74、CEP-1、citC1Ⅲ和中间丝相关蛋白抗体的荧光强度比对照者显著升高。最早检测到的抗体（Fibα591和Vim60-75）水平随时间而波动，在RA发病后仅轻度升高。抗Fibβ36-52， CEP-1和中间丝相关蛋白抗体频率逐渐增加，在RA首发症状出现前达到最高峰。抗citC1Ⅲ，Fibα573和Fibβ74抗体的频率在RA首发症状出现前仅轻度升高，但是在RA发病之后显著升高。与单独表达抗CEP-1或者Fibβ36-52抗体的个体相比，同时表达抗CEP-1和Fibβ36-52抗体个体（数据来自于距离RA发病的时间

研究发现，针对环瓜氨酸肽的免疫反应开始时受到抑制，但是，随着时间进展逐渐诱导出更严重的特异反应；同时，距离RA首发症状出现时间越近，抗体水平越高，特别是抗CEP-1，Fibβ36-52和中间丝相关蛋白抗体。

Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis.OBJECTIVEThe presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms.METHODSA case-control study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen α573 (Fibα573), Fibα591, Fibβ36-52, Fibβ72, Fibβ74, α-enolase (citrullinated α-enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 2-17 (Vim2-17), and Vim60-75, were analyzed using a microarray system.RESULTSThe fluorescence intensity of antibodies against Fibβ36-52, Fibβ74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls (PCONCLUSIONDevelopment of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fibβ36-52, and filaggrin, increasing during the predating time period closer to the onset of symptoms.