14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome

Primary Sjögren syndrome (PSS) is a chronic, autoimmune, and lymphoproliferative disease of the connective tissue. In patients with PSS, the risk of developing B-cell non-Hodgkin lymphoma (NHL) increases dramatically, with a prevalence of approximately 5%. The 14-3-3 protein isoforms are phospho-serin/phospho-threonine binding proteins associated with many malignant diseases. This study aimed to evaluate the relationship between disease activity parameters and markers predicting lymphoma development in patients with PSS and 14-3-3η proteins.

This study was designed as an analytical case-control study. A total of 57 PSS patients and 54 healthy volunteers were included in the study. The European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index (ESSDAI) was used to assess systemic disease activity in PSS. Receiver operating characteristic (ROC) analysis was used to test the diagnostic accuracy measures of the analytical results. Multivariable linear regression analysis was used to evaluate the effects of independent variables on the 14-3-3η protein.

The 14-3-3η protein serum levels were found to be significantly higher in PSS (2.72 [2.04-4.07]) than healthy controls (1.73 [1.41-2.43]) (P < 0.0001). A significant relationship was found between 14-3-3η protein levels and ESSDAI group (β = 0.385, 95%CI = 0.318-1.651, P = 0.005), hypocomplementemia (C3 or C4) (β = 0.223, 95% CI = 0.09-1.983, P = 0.048) and purpura (β = 0.252, 95% CI = 0.335-4.903, P = 0.022), which are accepted as lymphoma predictors. A significant correlation was found between PSS disease activity score ESSDAI and 14-33η protein (β = 0.496, 95% CI = 0.079-0.244, P = 0.0002).

14-3-3η proteins are potential candidates for diagnostic marker, marker of disease activity, and predictor of lymphoma in PSS patients.