Lymphomagenesis in Sjogren's syndrome: Predictive biomarkers towards precision medicine

Sjogren's syndrome (SS) is characterized by B cell hyperactivity documented by the production of plethora of autoantibodies and a strong tendency for NHL of B cell origin. Classical predictors of lymphoma have been already proposed and proved their validity, including clinical, serological and histopathologic biomarkers. The process of lymphomagenesis is multistep and encompasses mechanisms of antigen driven selection of the BCR with RF activity and various genetic contributors implicated in B cell proliferation, cell growth and cell cycle control, enhanced by a complex milieu of cytokines and trophic agents that are abundant within the inflammatory lesion of minor salivary glands of SS patients. Extensive efforts in the basic research field have revealed several novel biomarkers for lymphoma prediction while the major cellular and molecular mechanisms of evolutionary transition of B cells towards malignancy are under investigation. In this review, we present the current data regarding the newly proposed biomarkers for SS associated lymphoma prediction and a hypothetical model of lymphomagenesis based on the emerging data.