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非类风湿性关节炎疾病样本中抗环瓜氨酸肽阳性:是否依赖瓜氨酸?

Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not?

作者信息

Vannini A, Cheung K, Fusconi M, Stammen-Vogelzangs J, Drenth J P H, Dall'Aglio A C, Bianchi F B, Bakker-Jonges L E, van Venrooij W J, Pruijn G J M, Zendman A J W

机构信息

Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, and Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy.

出版信息

Ann Rheum Dis. 2007 Apr;66(4):511-6. doi: 10.1136/ard.2006.058933. Epub 2006 Sep 19.

DOI:10.1136/ard.2006.058933
PMID:16984940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1856034/
Abstract

BACKGROUND

Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum autoantibodies. Recently, in a large group of patients with AIH-1 without clear rheumatoid arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was scored.

OBJECTIVES

To characterise the citrulline-dependence of the observed anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without rheumatoid arthritis (mainly rheumatic diseases).

METHODS

Serum samples of 57 patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them reported as anti-CCP positive, were tested for citrulline-specific reactivity with a second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1 sera was also tested with a CCP1 ELISA (and arginine control).

RESULTS

The anti-CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87-93%) was citrulline-specific, whereas a relatively high percentage of AIH-1 samples (42-50%) turned out to be reactive in a citrulline-independent manner. The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high occurrence of citrulline-independent reactivity in AIH-1 samples.

CONCLUSIONS

In rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease sera, anti-CCP positivity is citrulline-dependent. However in some patients, particularly patients with AIH-1, citrulline-independent reactivity in the anti-CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver disease) should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.

摘要

背景

针对瓜氨酸化蛋白的抗体(如抗环瓜氨酸肽(CCP))对类风湿关节炎具有出色的诊断价值和良好的预后评估潜力。1型自身免疫性肝炎(AIH - 1)是一种以多种血清自身抗体为特征的慢性肝病。最近,在一大组无明确类风湿关节炎重叠的AIH - 1患者中,抗CCP2阳性率相对较高(9%)。

目的

明确AIH - 1血清以及其他无类风湿关节炎患者群体(主要为风湿性疾病)中观察到的抗CCP2阳性对瓜氨酸的依赖性。

方法

使用第二代抗CCP试剂盒,对57例AIH - 1患者和66例无类风湿关节炎患者(其中大多数报告为抗CCP阳性)的血清样本进行瓜氨酸特异性反应性检测,检测瓜氨酸化和相应的非瓜氨酸化(含精氨酸)抗原。还使用CCP1 ELISA(及精氨酸对照)对一部分AIH - 1血清进行检测。

结果

大多数非类风湿关节炎风湿性疾病样本(87 - 93%)的抗CCP2反应性是瓜氨酸特异性的,而相对较高比例的AIH - 1样本(42 - 50%)以不依赖瓜氨酸的方式产生反应。使用瓜氨酸化和非瓜氨酸化的CCP1肽证实了AIH - 1样本中存在高比例的不依赖瓜氨酸的反应性。

结论

在类风湿关节炎和大多数非类风湿关节炎风湿性疾病血清中,抗CCP阳性是瓜氨酸依赖性的。然而,在一些患者中,特别是AIH - 1患者,抗CCP2检测中可能出现不依赖瓜氨酸的反应性。因此,在非风湿性疾病(如肝病)中CCP检测呈阳性时应谨慎解读,最好随后用非瓜氨酸化抗原进行对照ELISA检测。

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