Burska Agata N, Neilan Jessica, Chisman Ruth E, Pitaksalee Rujiraporn, Hodgett Richard, Marzo-Ortega Helena, Conaghan Philip G, West Robert, Emery Paul, Ponchel Frederique
Leeds Institute of Rheumatic and Musculoskeletal Medicine and NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, and the Leeds Trust Teaching Hospital, Chapel Allerton Hospital, Leeds, UK.
Transplant Immunology Laboratory, St James' University Hospital, Leeds, UK.
Clin Exp Rheumatol. 2018 Jan-Feb;36(1):115-120. Epub 2017 Sep 15.
Despite the well-established value of currently used classification criteria for the early diagnosis of rheumatoid arthritis (RA) there is a constant demand for novel biomarkers notably in autoantibody-negative patients. Interleukin 7 (IL-7) has been reported as a candidate diagnostic biomarker based on ACR-1987 criteria. However, clinical practice has moved to using the EULAR 2010 classification criteria. Therefore, to advance the use of IL-7 alongside the RA biomarker pipeline, we repeated the original study in a new cohort.
255 patients were recruited. IL-7 was quantified by ELISA. Univariate and regression analyses were used to model RA diagnosis.
123 patients were diagnosed with RA (EULAR 2010) while 132 were classified as non-RA. In univariate analysis, RA was associated with autoantibodies and SE-positivity, higher joint counts, DAS28 (all p<0.001) and CRP (p=0.024). IL-7 was lower in RA (p=0.05). Logistic regression analysis in 227 patients with complete data set confirmed IL-7 was the second best predictive marker (p=0.035) following SJC (p=0.007) with good model fit (AUROC=0.889). A second model investigated 147 ACPA-negative patients: lower IL7 was the second best predictive marker (p=0.075) behind SJC (p=0.013).
This study validates our previous results from a UK cohort using EULAR 2010 criteria although the predictive power associated with IL-7 is lower than in the study using ACR 1987 criteria (both French/UK cohorts). IL-7 remains a potential biomarker for ACPA-negative RA although further validation with larger numbers of ACPA-negative patients is still needed notably to translate these results into clinical applicability.
尽管目前用于类风湿关节炎(RA)早期诊断的分类标准具有公认的价值,但对于新型生物标志物仍有持续需求,尤其是在自身抗体阴性的患者中。白细胞介素7(IL-7)已被报道为基于美国风湿病学会(ACR)1987年标准的候选诊断生物标志物。然而,临床实践已转向使用欧洲抗风湿病联盟(EULAR)2010年分类标准。因此,为了推进IL-7在RA生物标志物体系中的应用,我们在一个新队列中重复了原研究。
招募了255名患者。通过酶联免疫吸附测定(ELISA)对IL-7进行定量。采用单变量和回归分析对RA诊断进行建模。
123名患者被诊断为RA(EULAR 2010标准),而132名被归类为非RA。在单变量分析中,RA与自身抗体和SE阳性、更高的关节计数、疾病活动评分28(DAS28,均p<0.001)以及C反应蛋白(CRP,p=0.024)相关。RA患者的IL-7水平较低(p=0.05)。对227名具有完整数据集的患者进行逻辑回归分析证实,IL-7是仅次于关节肿胀计数(SJC,p=0.007)的第二佳预测标志物(p=0.035),模型拟合良好(曲线下面积=0.889)。第二个模型研究了147名抗环瓜氨酸肽抗体(ACPA)阴性的患者:较低的IL-7是仅次于SJC(p=0.013)的第二佳预测标志物(p=0.075)。
本研究使用EULAR 2010标准验证了我们之前来自英国队列的结果,尽管与IL-7相关的预测能力低于使用ACR 1987标准的研究(法国/英国队列)。IL-7仍然是ACPA阴性RA的潜在生物标志物,尽管仍需要对大量ACPA阴性患者进行进一步验证,尤其是将这些结果转化为临床适用性。