AB0302 The role of the biomarker 14–3–3 eta in rheumatoid arthritis: a review
Authors: S. Kilborn, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biomarkers are of much interest in rheumatoid arthritis (RA). Valid, reliable and convenient biomarkers, to detect early disease, predict severity and monitor treatment response are essential to achieving optimal outcomes. Several biomarkers have been suggested but are largely not validated. Validated measures of rheumatoid factor(RF), citrullination antibodies(ACPA), C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR) do not provide a complete picture. 14–3–3η, a protein from a family of highly conserved regulatory molecules, has promising data as a novel RA biomarker and is the focus of this review. <h3>Objectives</h3> This review aimed to identify the literature characterising 14–3–3η and its utility in RA. <h3>Methods</h3> Search terms 14–3–3η, biomarker and rheumatoid arthritis were used in Pubmed, Web of Science and Embase databases and reference lists of relevant papers were scanned. Inclusion criteria were confirmed RA, 14–3–3η and English language. <h3>Results</h3> Seven key papers were identified on 14–3–3η proteins<sup>1-6</sup> and one on 14–3–3η antibodies (14–3–3η-Ab)<sup>7</sup>. <b><i>Detecting RA:</i></b> 14–3–3η was elevated in patients with RA compared to healthy controls<sup>2,4</sup> and patients with other diseases (p&lt;0.001)<sup>4</sup>. Being positive for 14–3–3η (&gt;0.19 ng/mL) showed sensitivity and specificity of 63.3% and 92.6%<sup>4</sup> to detect RA, increasing to 91.7% and 99.6%, respectively when an ROC-determined optimal cut-off of 0.879 ng/mL was used<sup>2</sup>. When combined with current markers RF ±ACPA the detection capacity for early RA increased to 78% and for established RA to 96%, compared to 72% and 88%<sup>4</sup>, respectively for RF ±ACPA alone. Including the 14–3–3η-Ab further increased detection<sup>7</sup>. The 14–3–3η-Ab appeared at higher levels in early, treatment naïve RA, while no difference was seen in established RA compared to controls<sup>7</sup>. The 14–3–3η-Ab was not associated with inflammatory markers ESR or CRP<sup>7</sup>. Although higher levels of the 14–3–3η protein were detected in early RA (p&lt;0.05), rate of detection was higher in established RA<sup>2</sup>. <b><i>Predicting disease severity:</i></b> Baseline 14–3–3η status was associated with increased disease severity<sup>1,2,3,4,5</sup>, higher median DAS (6.3 vs 5.7, p=0.026) and HAQ scores (1.9 vs 1.0, p=0.001)<sup>4</sup>. Significant associations with baseline DAS28-ESR, CDAI and SDAI (p&lt;0.045 – p&lt;0.001) were also reported<sup>3</sup>. Physical symptoms are closely related to 14–3–3η levels<sup>2</sup>; patients achieving DAS28-ESR-defined remission had significantly lower levels than non-remitters<sup>3</sup>. Radiographic progression was significantly associated with higher 14–3–3η<sup>1 5</sup>, OR=6.2 (95%CI 1.3 to 30.2) in early RA and 2.5 (95%CI 1.0 to 1.4) in established RA<sup>5</sup>. Conflicting results on associations with existing markers ESR, CRP, RF, and ACPA have been reported<sup>1,2,3,4,5,6</sup>. <b><i>Treatment response:</i></b> 14–3–3η levels are dynamic with changing disease activity<sup>1,3</sup>. Also, pre-treatment 14–3–3η levels were an independent predictor of response to some therapies<sup>3</sup>. <h3>Conclusions</h3> 14–3–3η protein and Ab are promising biomarkers in RA diagnosis, disease severity and response to treatment. Future research characterising the protein in RA and its relationship with validated biomarkers and composite measures, and expanding on the 14–3–3η-Ab would be well directed. <h3>References</h3> [1] Arthritis Res Ther. 2016;18:37. [2] Clin Rheumatol. 2017;36(11):2581–87. [3] Arthritis Res Ther. 2015;17:280. [4] J Rheumatol. 2014;41(11):2104–13. [5] Arthritis Res Ther. 2014;16:R99. [6] Arthritis Res Ther. 2016;18:76. [7] J Rheumatol. 2015;42(9):1587–94. <h3>Disclosure of Interest</h3> None declared