Background Early diagnosis of rheumatoid arthritis (RA) and timely therapeutic intervention with disease modifying therapies (DMARDs) improves patient outcomes. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA) may not be present in early RA, therefore additional biomarkers for seronegative RA are of interest. It has been previously reported that serum 14-3-3eta is an early RA diagnostic biomarker that complements RF and anti-CCP and marks response to anti-TNF therapy.
Objectives We investigated 14-3-3eta plasma expression in an early RA cohort, its modifiability with DMARD therapy and relationship with change in clinical variables.
Methods Banked plasma samples from 62 early RA patients in the Reade cohort were evaluated by ELISA for 14-3-3eta expression at diagnosis (baseline) and at 1 year. Mean age was 54 years, 79% were female, median duration of symptoms was 4 months (IQR 3-7), 61% (38 of 62) were ACPA positive and patients were therapy naïve at baseline and only on standard DMARDS over the course of 1 year. To evaluate the difference in 14-3-3 eta expression from baseline to Year 1, a paired t-test and the Wilcoxon matched pairs signed rank test were performed. The absolute changes (Δ) in Disease Activity Score (DAS28) and its components Tender Joint Count (TJC), Swollen Joint Count (SJC), Patient Global Assessment and ESR were calculated from baseline to Year 1, as well as Physician Global Assessment and Visual Analog Scale (VAS) Pain. Pearson correlations were run to evaluate relationships between Δ14-3-3 eta and the change in each of these variables.
Results Of the 62 early RA patients, 38 (61%) were positive for 14-3-3 eta using the reported cut-off of 0.19ng/ml for diagnosis, 8 (21%) of which were ACPA negative. Plasma concentrations of 14-3-3 eta changed with an overall mean decrease from baseline to Year 1 of 4.66 to 3.01ng/ml and medians of 0.67 to 0.38ng/ml. The paired t-test delivered a p-value of 0.03 and for the Wilcoxon signed rank test, p=0.006. Of the 62 patients, 28 (45%) had a decrease and 34 (55%) had an increase or no change (no decrease) in 14-3-3 eta plasma concentrations from baseline to Year 1. The median improvements in the clinical measures was greater in the group that had a decrease in 14-3-3 eta versus no decrease; ΔPhysician Global Assessment was statistically significant (44.5 vs. 24.0; p=0.016), ΔDAS-28 (2.3 vs. 1.5; p=0.055), ΔTJC (5.0 vs. 2.5; p=0.096), ΔPatient Global (35.0 vs. 14.0; p=0.15), ΔSJC (6.5 vs. 4.0; p=0.24), and ΔVAS (27.0 vs. 13.0; p=0.42). Pearson correlations between the Δ14-3-3 eta and the change in each of these clinical variables at one year did not return any significant relationships, including no correlation with ΔCRP, r=-0.065, p=0.62.
Conclusions 14-3-3 eta is an early RA plasma and serum marker that is modifiable with standard DMARD therapy. Its changes are independent of CRP and correspond with improvement in clinical variables at one year following diagnosis. Changes in 14-3-3 eta plasma concentrations early along the treatment course, within 3 months of treatment initiation, should be investigated for therapy response monitoring utility with standard DMARDs.
Disclosure of Interest K. Britsemmer: None Declared, W. P. Maksymowych: None Declared, D. van Schaardenburg: None Declared, A. Marotta Employee of: Augurex Life Sciences Corp