Serum 14-3-3 eta is a Novel Marker that Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis JOURNAL OF RHEUMATOLOGY Maksymowych, W. P., Naides, S. J., Bykerk, V., Siminovitch, K. A., van Schaardenburg, D., Boers, M., Landewe, R., van der Heijde, D., Tak, P., Genovese, M. C., Weinblatt, M. E., Keystone, E. C., Zhukov, O. S., Abolhosn, R. W., Popov, J. M., Britsemmer, K., van Kuijk, A. W., Marotta, A. 2014; 41 (11): 2104-2113


Serum 14-3-3? is a novel joint-derived proinflammatory mediator implicated in the pathogenesis of rheumatoid arthritis (RA). In our study, we assessed the diagnostic utility of 14-3-3? and its association with standard clinical and serological measures.A quantitative ELISA was used to assess 14-3-3? 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 14-3-3?, and the likelihood ratios (LR) for RA were determined through receiver-operator curve analysis. The incremental value of adding 14-3-3? to anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in diagnosing early and established RA was assessed.Serum 14-3-3? differentiated established patients with RA from healthy individuals and all controls (p<0.0001). A serum 14-3-3? 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 14-3-3?, 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 14-3-3? positivity were used in combination, 77 of the 99 patients (78%) with early RA were positive for any 1 of the 3 markers. Serum 14-3-3? did not correlate with C-reactive protein, erythrocyte sedimentation rate, or Disease Activity Score, but patients who were 14-3-3?-positive had significantly worse disease.Serum 14-3-3? 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.

View details for DOI 10.3899/jrheum.131446

View details for Web of Science ID 000344598900006

View details for PubMedID 25128504