Soluble 14-3-3? - A Personalised Rheumatoid Arthritis Patient Management Strategy

Rheumatoid Arthritis (RA) is a heterogenous disease that affects 1.5% of the population. Similar to cancer, early detection coupled with an effective treatment strategy can significantly improve patient outcomes. In the advent of new classes of RA therapies, there is an impetus to identify new serological markers that mark risk of RA development, prognosis and therapy response. 14-3-3 eta (?) is a new RA marker that is available for clinical use in the US through Quest Diagnostics. 14-3-3? is one of 7 members of the 14-3-3 family and is specifically present in the serum of patients with RA and erosive psoriatic arthritis (PsA). In the healthy state, these proteins reside within the intracellular space governing various biological processes including proliferation, differentiation and metabolism. Increased expression of different 14-3-3 isoforms correspond with worse prognosis in certain cancers and neurological disorders. In RA, the 14-3-3? protein is specifically externalized and can be measured in serum, making it a useful clinical serum marker. When 14-3-3? exists in the extracellular environment, it behaves as a soluble ligand inducing factors that drive inflammation and joint damage also making it a novel therapeutic target. This presentation will describe the discovery of 14-3-3? in arthritis, its development pathway and the biomarker's clinical utility. We will discuss how the 14-3-3? biomarker pipeline has evolved from the protein R&D programs into a 14-3-3? biomarker suite that serves as a direct companion to a first-in-class RA personalized medicine drug target.