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

• Published in: Journal of rheumatology Vol. 41; no. 11; p. 2104
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Canada 01.11.2014
• Subjects: 14-3-3 Proteins - blood; Adult; Area Under Curve; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - physiopathology; Biomarkers - blood; Canada; Case-Control Studies; Cohort Studies; Disease Progression; Enzyme-Linked Immunosorbent Assay - methods; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Prognosis; Reference Values; Rheumatoid Factor - blood; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Canada; C-REACTIVE PROTEIN; RHEUMATOID ARTHRITIS; SERUM 14-3-3η; ANTICITRULLINATED PROTEIN ANTIBODIES; BIOMARKER; RHEUMATOID FACTOR
• ISSN: 0315-162X
• DOI: 10.3899/jrheum.131446

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. 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. 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. 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.