14-3-3 proteins represent a highly conserved seven-member family of ubiquitously expressed intracellular chaperonins that perform a broad range of signaling functions. The 14-3-3 eta (η) protein is an emerging diagnostic and prognostic biomarker for RA driving inflammation and joint erosion1. Elevated levels of the η isoform have been reported in synovial fluid and serum from patients with joint inflammation2, but not with other diseases including psoriasis, osteoporosis, SLE, Crohn's and MS. Here we evaluate the impact of this RA-associated biomarker on the levels of clinically relevant biomarkers across a panel of human primary cell-based disease models3. The biomarker activity profile for 14-3-3η is consistent with activation of B cell responses that correlates with pro-inflammatory activity associated with disease-relevant biomarkers. This data supports the hypothesis that 14-3-3η may serve both as a diagnostic marker in early RA as well as an important target for therapeutic intervention.