PT  - JOURNAL ARTICLE
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 C. Keystone
AU  - Olga S. Zhukov
AU  - Rania W. Abolhosn
AU  - Joanna M. Popov
AU  - Karin Britsemmer
AU  - Arno W. van Kuijk
AU  - Anthony Marotta
TI  - Serum 14-3-3η is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis
AID  - 10.3899/jrheum.131446
DP  - 2014 Nov 01
TA  - The Journal of Rheumatology
PG  - 2104--2113
VI  - 41
IP  - 11
4099  - http://www.jrheum.org/content/41/11/2104.short
4100  - http://www.jrheum.org/content/41/11/2104.full
SO  - J Rheumatol2014 Nov 01; 41
AB  - 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.