TY - JOUR T1 - Serum 14-3-3η is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.131446 SP - jrheum.131446 AU - Walter P. Maksymowych AU - Stanley J. Naides AU - Vivian Bykerk AU - Katherine A. Siminovitch AU - Dirkjan van Schaardenburg AU - Maarten Boers AU - Robert Landewé AU - Désirée van der Heijde AU - Paul-P. Tak AU - Mark C. Genovese AU - Michael E. Weinblatt AU - Edward Keystone AU - Olga S. Zhukov AU - Rania W. Abolhosn AU - Joanna M. Popov AU - Karin Britsemmer AU - Arno W. van Kuijk AU - Anthony Marotta Y1 - 2014/08/15 UR - http://www.jrheum.org/content/early/2014/08/09/jrheum.131446.abstract N2 - 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. ER -