血清14-3-3η是一种新型标志物，可补充当前的血清学检测方法，以提高类风湿性关节炎患者的检测率。

Serum 14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis.

作者信息

Maksymowych Walter P, Naides Stanley J, Bykerk Vivian, Siminovitch Katherine A, van Schaardenburg Dirkjan, Boers Maarten, Landewé Robert, van der Heijde Désirée, Tak Paul-P, Genovese Mark C, Weinblatt Michael E, Keystone Edward C, Zhukov Olga S, Abolhosn Rania W, Popov Joanna M, Britsemmer Karin, van Kuijk Arno W, Marotta Anthony

机构信息

From the University of Alberta, Edmonton, Alberta; Augurex Life Sciences Corp., North Vancouver, British Columbia; Mount Sinai Hospital, Toronto, Ontario, Canada; Quest Diagnostics Nichols Institute, San Juan Capistrano; Stanford University Medical Center, Palo Alto, California; Hospital for Special Surgery, New York, New York; Brigham and Women's Hospital, Boston, Massachusetts, USA; Vrije Universiteit University Medical Center; Academic Medical Center/University of Amsterdam; Jan van Breemen Research Institute, Reade organization, Amsterdam; the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; University of Cambridge, Cambridge; GlaxoSmithKline, Stevenage, UK.W.P. Maksymowych, MD, Professor of Medicine, University of Alberta; S.J. Naides, MD, Quest Diagnostics Nichols Institute; V. Bykerk, MD, Hospital for Special Surgery; K.A. Siminovitch, MD, Mount Sinai Hospital; D. van Schaardenburg, MD, Jan van Breemen Research Institute; M. Boers, MD, Vrije Universiteit University Medical Center; R. Landewé, MD, Academic Medical Center/University of Amsterdam; D. van der Heijde, MD, Department of Rheumatology, Leiden University Medical Center; P-P. Tak, MD, Academic Medical Center/University of Amsterdam, University of Cambridge, GlaxoSmithKline; M.C. Genovese, MD, Stanford University Medical Center; M.E. Weinblatt, MD, Brigham and Women's Hospital; E.C. Keystone, MD, Mount Sinai Hospital; O.S. Zhukov, MS; R.W. Abolhosn, BS; J.M. Popov, MD, PhD, Quest Diagnostics Nichols Institute; K. Britsemmer, MD, Jan van Breemen Research Institute; A.W. van Kuijk, MD, Academic Medical Center/University of Amsterdam; A. Marotta, PhD, Augurex Life Sciences Corp.

出版信息

J Rheumatol. 2014 Nov;41(11):2104-13. doi: 10.3899/jrheum.131446. Epub 2014 Aug 15.

DOI:10.3899/jrheum.131446

PMID:25128504

Abstract

OBJECTIVE

Serum 14-3-3η is a novel joint-derived proinflammatory mediator implicated in the pathogenesis of rheumatoid arthritis (RA). In our study, we assessed the diagnostic utility of 14-3-3η and its association with standard clinical and serological measures.

METHODS

A quantitative ELISA was used to assess 14-3-3η levels. Early (n=99) and established patients with RA (n=135) were compared to all controls (n=385), including healthy subjects (n=189). The sensitivity, specificity, positive and negative predictive values of 14-3-3η, and the likelihood ratios (LR) for RA were determined through receiver-operator curve analysis. The incremental value of adding 14-3-3η to anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in diagnosing early and established RA was assessed.

RESULTS

Serum 14-3-3η differentiated established patients with RA from healthy individuals and all controls (p<0.0001). A serum 14-3-3η cutoff of ≥0.19 ng/ml delivered a sensitivity and specificity of 77% and 93%, respectively, with corresponding LR positivity of 10.4. At this cutoff in early RA, 64% of patients with early RA were positive for 14-3-3η, with a corresponding specificity of 93% (LR+ of 8.6), while 59% and 57% were positive for ACPA or RF, respectively. When ACPA, RF, and 14-3-3η positivity were used in combination, 77 of the 99 patients (78%) with early RA were positive for any 1 of the 3 markers. Serum 14-3-3η did not correlate with C-reactive protein, erythrocyte sedimentation rate, or Disease Activity Score, but patients who were 14-3-3η-positive had significantly worse disease.

CONCLUSION

Serum 14-3-3η is a novel RA mechanistic marker that is highly specific, associated with worse disease, and complements current markers, enabling a more accurate diagnosis of RA.

摘要

目的

血清14-3-3η是一种新的关节源性促炎介质，与类风湿关节炎（RA）的发病机制有关。在我们的研究中，我们评估了14-3-3η的诊断效用及其与标准临床和血清学指标的关联。

方法

采用定量ELISA法评估14-3-3η水平。将早期RA患者（n = 99）和确诊RA患者（n = 135）与所有对照（n = 385）进行比较，包括健康受试者（n = 189）。通过受试者工作特征曲线分析确定14-3-3η的敏感性、特异性、阳性和阴性预测值以及RA的似然比（LR）。评估在诊断早期和确诊RA时，将14-3-3η添加到抗瓜氨酸化蛋白抗体（ACPA）和类风湿因子（RF）中的增加值。

结果

血清14-3-3η可将确诊的RA患者与健康个体及所有对照区分开来（p<0.0001）。血清14-3-3η临界值≥0.19 ng/ml时，敏感性和特异性分别为77%和93%，相应的阳性似然比为10.4。在早期RA中，以此临界值判断，64%的早期RA患者14-3-3η呈阳性，相应的特异性为93%（阳性似然比为8.6），而ACPA或RF呈阳性的患者分别为59%和57%。当联合使用ACPA、RF和14-3-3η阳性结果时，99例早期RA患者中有77例（78%）的3种标志物中任一种呈阳性。血清14-3-3η与C反应蛋白、红细胞沉降率或疾病活动评分无关，但14-3-3η阳性的患者疾病明显更严重。