Background Early RA diagnosis and timely treatment can improve patient outcomes. Markers are needed to identify patients with early disease who are at high-risk of joint damage progression. Current clinical and serological variables only explain approximately 32% of the risk1, underscoring the need for new disease specific markers that add to the rheumatologist's prognostic armamentarium. 14-3-3η is a mechanistic, joint-derived, serological marker that potently induces cytokines and joint damage factors, directly implicating it in RA disease pathophysiology.
Objectives The aim of this study was to determine whether 14-3-3η serum levels are predictive of joint damage progression in this recent-onset polyarthritis cohort.
Methods Serum 14-3-3η levels were measured at baseline in 33 patients with recent-onset polyarthritis (EPA) from the Sherbrooke EUPA cohort. Patients were rapidly treated with conventional DMARDs to achieve clinical remission; 3 also received biologic agents. Radiographic progression was defined as a change in Sharp/van der Heijde score (ΔSHS) ≥1 at 30 months. Differences in median 14-3-3η between progressors and non-progressors were analyzed by 2-tailed Mann-Whitney U-test. The relationship between serum 14-3-3η and radiographic progression was investigated by univariate analysis using 14-3-3η cut-offs selected as follows: the manufacturer's (Augurex 14-3-3η ELISA) reported diagnostic cut-off ≥0.19 ng/ml and 2X that,0.40 ng/ml. Stepwise multivariate analyses were performed to determine 14-3-3η's contribution to predicting joint damage progression amongst other clinical and serological variables, including titres of 14-3-3η, RF, CCP, CRP, ESR, together with age, gender and disease duration.
Results Median age was 51 years and 70% were female. Twenty of the 33 (61%) patients progressed after 30 months while 13 did not. Progressors had a median (IQR) ΔSHS of 7.0 (3.3-12.8). 14-3-3η and RF median (IQR) levels at baseline were significantly higher in progressors than non-progressors [2.7ng/ml (0.1-15.9) vs. 0.1ng/ml (0.1–0.2), p=0.006] and [160 IU/ml (40-320) vs. 0 IU/ml (0–160), p=0.006]. Univariate analyses revealed that RF positivity was associated with radiographic progression; relative risk (RR) of 2.8 (95%CI: 1.1-7.6), p=0.035. 14-3-3η, at both cut-offs, was also associated with radiographic progression; ≥0.19 ng/ml, RR=2.0 (1.1-3.7), p=0.02; ≥0.40 ng/ml, and RR=2.2 (1.2-4.1), p=0.006, respectively. 14-3-3η titres were associated with joint damage progression, LR of 5.2, p=0.02. Stepwise multivariate analysis returned 14-3-3η titres (LR=5.6, p=0.02), ESR (LR=6.4, p=0.01), CRP (LR=4.6, p=0.03) and gender (LR=4.4, p=0.04) as independent predictors of radiographic progression, together informing 29.4% of the total variance (R2) in radiographic progression. When 14-3-3η titres were excluded, the R2 for ESR, CRP and gender was 16.8%, indicating that of the 4 significant variables, 14-3-3η accounted for 43% (12.6%/29.4%) of the model's predictive power.
Conclusions Serum 14-3-3η in recent-onset polyarthritis was associated with an increased risk of joint damage progression at 30 months. When added to current prognostic markers, is 14-3-3η an independent predictor of radiographic progression adding 43% to their prognostic predictive power.
de Rooy DPC et al. Rheum. 2011. 50:93.
Disclosure of Interest G. Boire: None declared, N. Carrier: None declared, A. de Brum-Fernandes: None declared, P. Liang: None declared, A. Masetto: None declared, Y. Gui Employee of: Augurex Life Sciences Corp, M. Murphy Employee of: Augurex Life Sciences Corp, W. Maksymowych Consultant for: Augurex Life Sciences Corp, A. Marotta Employee of: Augurex Life Sciences Corp
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.