In the healthy state, 14-3-3η (eta) protein is a highly-conserved and ubiquitously expressed intracellular protein. In RA, through what is understood to be an exosomal-mediated process, 14-3-3η is released outside of cells and is present in the extracellular space (synovial fluid and blood). Its extracellular expression is believed to “switch on” immune cells, causing them to release factors that are involved in promoting inflammation and joint destruction. The image below illustrates the intracellular pathways that are activated, leading to the upregulation of deleterious factors that perpetuate disease.

While a positive 14-3-3η test may assist with patient referral to a specialist for a prompt RA diagnosis, higher levels indicate that more joint destructive factors are present thereby increasing the aggressiveness of the disease. 14-3-3η levels can change over time, and studies have shown that low and decreasing levels are associated with a more favorable outcome.