van Heemst Jurgen, Trouw Leendert A, Nogueira Leonor, van Steenbergen Hanna W, van der Helm-van Mil Annette H M, Allaart Cornelia F, Serre Guy, Holmdahl Rikard, Huizinga Tom W J, Toes René E M, van der Woude Diane
Department of Rheumatology C1-R, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, Leiden, 2300 RC, The Netherlands.
Laboratory of Epidermis differentiation and Rheumatoid Autoimmunity, Centre National de la Recherché Scientifique, Avenue de Grande-Bretagne 330, TSA 40031, Toulouse, 31059, Cedex 9, France.
Arthritis Res Ther. 2015 Oct 5;17:276. doi: 10.1186/s13075-015-0786-z.
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.
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.
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 %).
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.
最近，已有可利用不同瓜氨酸化肽同时分析多种抗瓜氨酸化蛋白抗体（ACPA）反应性的检测方法。此类检测方法专为探索性研究而设计。如果了解多重检测在早期关节炎情况下的诊断和预后价值，并且对根据三种常用商业ACPA检测为阴性的多重阳性患者进行特征描述，那么对阳性抗体反应性的解读将最为准确。
我们使用赛默飞世尔科技公司的免疫捕获ISAC（免疫固相过敏原芯片）系统，这是一种可测定对11种瓜氨酸化肽反应性的多重检测方法，分析了来自两个独立队列的195名健康对照者和1282名早期关节炎患者的血清/血浆：莱顿早期关节炎诊所（n = 1013）和IMPROVED（n = 269）队列。研究结果主要与抗瓜氨酸化环肽2（抗CCP - 2）检测结果进行比较，但也与抗CCP - 3和抗突变瓜氨酸化波形蛋白（抗MCV）检测结果进行比较。评估了ACPA反应性与患者特征、风险因素（共同表位、吸烟）和疾病结局（未分化关节炎进展为类风湿关节炎（RA）以及关节破坏的严重程度）之间的关联。
在多重检测中，31%的抗CCP - 2阴性RA患者对瓜氨酸化肽有反应性。与抗CCP - 2阳性RA患者相比，这些患者对更有限的肽库有阳性信号（中位数分别为1和5）。在抗CCP - 2阴性患者中，多重检测所检测到的ACPA反应性与已知风险因素或临床或预后参数无显著关联。抗CCP - 2阴性RA患者中多重肽呈阳性的血清频率与非RA关节炎患者的频率相当（27%）。
当前多重检测系统检测到的额外瓜氨酸肽反应性未达到具有RA特异性的显著效能。对于商业ACPA检测为阴性的关节炎患者，该多重检测系统检测到的残余瓜氨酸反应性的存在需要谨慎解读。
