AB0296 14–3–3eta positivity is associated with higher rheumatoid arthritis disease activity measured by multi-biomarker disease activity assay

Background Early diagnosis of rheumatoid arthritis (RA) is crucial but recognition of its disease activity and prognosis can help tailor treatment for patients in order to avoid debilitating consequences. 14–3–3eta has been described to have diagnostic utility as a biomarker of RA; however its use as prognostic factor is still under investigation.1 The η (eta) isoform is one of seven from the 14–3–3 family of regulatory proteins and is expressed extracellularly in much higher concentrations in the synovial fluid and serum of patients with RA. A multiple-biomarker disease activity (MBDA) score was recently introduced; 396 candidate cytokines and biomarkers were narrowed to twelve, correlating with disease activity. Objectives The purpose of our study was to investigate if 14–3–3η can be used as a prognostic factor and if it was associated with higher disease activity in RA patients. We compared the positivity of 14–3–3η in those with low, moderate, and high disease activity based on MBDA scores. In addition, as MBDA scores provide individual biomarker levels, we wanted to determine if there was a correlation between 14–3–3η and specific biomarker patterns. Methods A retrospective chart review was conducted on 70 RA patients (satisfied the 2010 ACR diagnostic criteria) at an outpatient rheumatology clinic in an inner-city population. Serum 14–3–3η protein was measured by ELISA with a positive threshold range (Quest Diagnostic) of 0.2 ng/mL. The MBDA scoring scale was 1–29 for low disease activity, 30–44 for moderate and 45–100 for high. The t-test was used to analyse for a significant difference in MBDA scores as well as individual biomarker levels in 14–3–3η positive patients. Results Of the 70 RA patients, 37 were 14–3–3η positive and 33 were negative. Thirty (81%) of 14–3–3η positive patients were on at least one DMARD compared to 16 (48.5%) of negative patients. The mean and median MBDA scores of 14–3–3η positive patients were 49.4 and 47, while negative patients’ scores were 36.9 and 38, respectively (p=0.002). Thus, 14–3–3η positive patients had high disease activity while 14–3–3η negative patients had moderate disease activity. Mean levels of matrix metalloproteinase 3 (MMP-3), serum amyloid A (SAA), and CRP in 14–3–3η positive versus negative were 52.3 ng/mL and 28.4 ng/mL (p=0.01), 24.3 mg/mL and 6.96 mg/mL (p=0.02), and 21.5 mg/L and 9.82 mg/L (p=0.02), respectively. Conclusions 14–3–3η positive RA patients have higher disease activity based on MBDA score and are associated with higher levels of MMP-3, SAA, and CRP. MMP-3 is associated with joint destruction through degradation of the components of extracellular matrix in the synovial joint. SAA and CRP are acute phase reactants but SAA has been linked with increased cardiovascular and renal disease in RA patients. 14–3–3η positive patients should be treated aggressively to decrease disease activity and limit extra-articular manifestations.2 Reference [1] Maksymowych W, Naides S, Bykerk V, Siminovitch K, et al. Serum 14–3–3η is a Novel Marker that Complements Current Serological Measurements to Enhane Detection of Patients with Rheumatoid Arthritis. J Rheumatol2014;41:2104–2113. Disclosure of Interest None declared