An investigation of the added value of an ACPA multiplex assay in an early rheumatoid arthritis setting
An investigation of the added value of an ACPA multiplex assay in an early rheumatoid arthritis setting
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DOI：
10.1186/s13075-015-0786-z
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发表时间：
2015-10-05
影响因子：
4.9
通讯作者：
van der Woude, Diane
中科院分区：
文献类型：
--
作者：
van Heemst, Jurgen;Trouw, Leendert A.;van der Woude, Diane
简介：最近，阵列已经可用，允许同时分析几种抗瓜氨酸化蛋白抗体（ACPA）的反应性使用不同的瓜氨酸化肽。这种检测是为探索性研究设计的。如果多重抗体阵列在早期关节炎的诊断和预后价值是已知的，并且根据三种常用的商业ACPA测定结果为阴性的多重抗体阳性患者具有特征，则可以最好地解释抗体阳性反应。方法：使用Thermo Scientific公司的ImmunoCap ISAC（免疫固相过敏原芯片）系统（一种多路阵列，可测定对11种citrullinated肽的反应性），我们分析了来自两个独立队列的195名健康对照和1282名早期关节炎患者的血清/血浆：Leiden早期关节炎诊所（n = 1013）和IMPROVED队列（n = 269）。结果主要与抗瓜氨酸环肽2（抗ccp -2）试验的结果进行比较，也与抗ccp -3和抗突变瓜氨酸波形蛋白（抗mcv）试验的结果进行比较。评估ACPA反应性与患者特征、危险因素（共享表位、吸烟）和疾病结局（未分化关节炎进展为类风湿性关节炎（RA）和关节破坏严重程度）之间的关系。结果：在多重试验中，31%的抗ccp -2阴性RA患者对瓜氨酸肽表现出反应性。与抗ccp -2阳性RA患者相比，这些患者在更有限的肽库中有阳性信号（中位数为1对5）。在抗ccp -2阴性的患者中，多重阵列检测到的ACPA反应性与已知的危险因素或临床或预后参数没有显著相关性。抗ccp -2阴性RA患者血清中多肽阳性的频率与非RA关节炎患者的频率相当（27%）。结论：目前的复合系统检测到的添加瓜氨酸肽反应性没有达到显著的ra特异性。在商业ACPA检测为阴性的关节炎患者中，该多重系统检测到残留瓜氨酸反应性的存在需要谨慎解释。
Introduction: Recently, arrays have become available that allow the simultaneous analysis of several anti-citrullinated protein antibody (ACPA) reactivities using distinct citrullinated peptides. Such assays are designed for exploratory studies. The interpretation of positive antibody reactivities can best be made if the diagnostic and prognostic value of a multiplex array in an early arthritis setting is known and if the multiplex-positive patients who are negative according to three commonly used commercial ACPA assays are characterized.Methods: Using Thermo Scientific's ImmunoCap ISAC (Immuno Solid-phase Allergen Chip) system, a multiplexed array that determines reactivities to 11 citrullinated peptides, we analysed serum/plasma of 195 healthy controls and 1282 early arthritis patients from two independent cohorts: the Leiden Early Arthritis Clinic (n = 1013) and the IMPROVED (n = 269) cohort. Findings were compared with results primarily of the anti-citrullinated cyclic peptide 2 (anti-CCP-2) assay but also with anti-CCP-3 and anti-mutated citrullinated vimentin (anti-MCV) assays. The associations between ACPA reactivities and patient characteristics, risk factors (shared epitope, smoking) and disease outcomes (progression of undifferentiated arthritis to rheumatoid arthritis (RA) and severity of joint destruction) were assessed.Results: Thirty-one percent of anti-CCP-2-negative RA patients displayed reactivity toward citrullinated peptides in the multiplex assay. These patients had a positive signal toward a more restricted peptide repertoire than anti-CCP-2-positive RA patients (median of 1 versus 5). Within anti-CCP-2-negative patients, ACPA reactivity as detected by multiplex array was not significantly associated with known risk factors or clinical or prognostic parameters. The frequency of sera from anti-CCP-2-negative RA patients who were positive for the multiplexed peptides was comparable to the frequency in non-RA arthritic patients (27 %).Conclusions: Additive citrulline peptide reactivities detected by the current multiplex system did not reach significant power to be RA-specific. The presence of residual citrulline reactivities detected by this multiplex system in arthritis patients who are negative in commercial ACPA assays needs to be interpreted with caution.