Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis
Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis
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DOI：
10.1186/1546-0096-9-8
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发表时间：
2011-03-25
影响因子：
2.5
通讯作者：
Moore, Terry L.
中科院分区：
文献类型：
--
作者：
Gilliam, Brooke E.;Reed, Melinda R.;Moore, Terry L.
背景资料：几项研究指出，测量抗环瓜氨酸肽（CCP）抗体在幼年特发性关节炎（JIA）中的重要性，作为破坏性疾病的重要指标，如类风湿性关节炎（RA）。虽然抗CCP抗体在RA和JIA中的作用已得到更好的理解，但这种修饰的靶蛋白的身份仍然难以捉摸。在这项研究中，我们评估了血清中的各种亚型的JIA患者调查存在的抗脱亚胺（瓜氨酸）纤维蛋白原和抗瓜氨酸α-烯醇化酶抗体，以及它们与RF和抗CCP抗体isotypes.Methods：血清中获得96 JIA患者，19例系统性红斑狼疮（SLE）患者，和10名健康儿童。通过酶联免疫吸附试验（ELISA）测定所有血清中抗瓜氨酸化和天然纤维蛋白原和α-烯醇化酶的抗体。此外，通过ELISA测定所有血清的抗CCP抗体同种型和类风湿因子（RF）同种型。还研究了抗瓜氨酸纤维蛋白原和抗α-烯醇化酶抗体与疾病活动性和关节损伤之间的关系。使用斯皮尔曼rho相关系数将所有结果与临床和实验室参数进行相关性分析。采用多元Logistic回归分析，以确定哪些变量与关节糜烂和诊断JIA.Results：31例JIA患者（32%）表现出瓜氨酸纤维蛋白原和9（9%）瓜氨酸α-烯醇化酶的反应。对瓜氨酸纤维蛋白原和α-烯醇化酶的反应主要见于IgM RF阳性的多发性关节炎患者。与JIA患者相比，14名JIA患者对天然α-烯醇化酶产生反应，并且更高比例的SLE患者对瓜氨酸化α-烯醇化酶产生反应。抗瓜氨酸纤维蛋白原抗体与IgG抗CCP抗体和伊加和IgM RF的存在相关。抗瓜氨酸化α-烯醇化酶抗体的存在与伊加抗CCP抗体相关。与对照组相比，IgG抗CCP抗体与关节损伤显著相关，抗瓜氨酸纤维蛋白原抗体与JIA密切相关。抗瓜氨酸纤维蛋白原抗体对IgM RF阳性多关节JIA表现出高敏感性（81%）。结论：JIA患者血清中抗瓜氨酸纤维蛋白原抗体具有较强的反应性，对JIA具有较高的敏感性和特异性，主要见于IgM RF阳性的多发性关节炎患者。纤维蛋白原是瓜氨酸在JIA中的几种蛋白质靶点之一。
Background: Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated alpha-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.Methods: Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and alpha-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-alpha-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.Results: Thirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated alpha-enolase. Reactivity to citrullinated fibrinogen and alpha-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native alpha-enolase and a higher percentage of SLE patients reacted with citrullinated alpha-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated alpha-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.Conclusions: JIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.