Background/Purpose: The 14-3-3 family of conserved regulatory proteins consists of seven isoforms: α/β, γ, δ/ζ, ε, η, θ/τ and σ. These proteins exist as intracellular adapters that interact with more than 200 intracellular proteins to modulate their activities. Extracellular 14-3-3η at concentrations found in patient serum activates key signalling cascades and induces factors associated with Rheumatoid Arthritis (RA) pathogenesis.¹ The purpose of this study was to determine if 14-3-3η serum levels are additive to available RA-associated autoantibodies to identify RA patients in a cohort of recent-onset polyarthritis cohort (EPA).

Methods: Using the manufacturer’s (Augurex 14-3-3η) ELISA, serum 14-3-3η levels were measured at baseline in 331 patients with EPA from the Sherbrooke EUPA cohort. All 331 had completed a follow up of at least 5 years. Patients were rapidly and intensively treated with DMARDs and/or biologics to achieve clinical remission defined as 0 swollen joint among 66. The manufacturer’s reported diagnostic cut-off of ≥0.19 ng/ml was used. Anti-CCP2 (EuroImmun and Inova Diagnostics) and IgM RF (RapiTex, Dade-Behring) were determined using commercial assays and Anti-Sa/citrullinated vimentin (Sa), using an in-house assay previously described.²

Results: Median age was 60 y.o. and 62% were female; median time of symptom duration was 4 months. Up to 92% were treated with DMARDs between baseline and the 18-month follow up; 23 also received biologic agents over that period. 14-3-3η was positive at baseline in 153 (46%) of patients and RF, anti-CCP2 and anti-Sa were positive respectively in 146 (44%), 132 (39.9%) and 73 (22%). When 14-3-3η protein was combined with antibodies, the proportion of patients with at least one positive test increased to 54.8% (RF or 14-3-3η), 55% (anti-CCP2 or 14-3-3η) and 49.7% (anti-Sa or 14-3-3η), corresponding to an incremental benefit in sensitivity of 25%, 38% and 126%, respectively. When combining 14-3-3η with all 3 antibodies, the number (proportion) of positive patients for at least one marker increased from 164 (51.0%) to 194 (58.6%).

Conclusion: Serum 14-3-3η positive status in recent-onset polyarthritis adds significant sensitivity to currently available RA-associated antibodies. Since higher 14-3-3η titres are associated with an increased risk of joint damage progression, our data support measuring it in early inflammatory polyarthritis to assist with patient stratification.

References: ¹Maksymowych et al. Arthritis Research & Therapy 2014, 16:R99; ²Boire G et al. 2005. Arthritis Research & Therapy, 7:R592-R603

ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-14-3-3-serum-protein-levels-increase-ra-confirmation-rates-in-recent-onset-polyarthritis-patients/