The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjögren's syndrome

Systemic autoimmune diseases, such as Sjögren's syndrome (SS), are characterized by a complex aetiology with multiple pathogenic factors. In SS, disturbed B-cell biology and humoral immunity including B-cell-activating factor (BAFF)-mediated processes have been described. Dysregulated BAFF expression has been described to lead to disease progression and perpetuation of humoral autoimmunity. Moreover, BAFF has been proposed to contribute to the development of B-cell malignancies. In this review, we summarize the current knowledge on BAFF with regard to SS pathology and discuss special features such as germinal centre (GC) formation and lymphomagenesis. Locally, in SS salivary glands, the reduced level of apoptosis among BAFF-expressing cells might lead to longer-existing BAFF expression and thereby maintain signalling for tissue-infiltrating B cells to proliferate and supposedly to become autoantibody-producing plasma cells. We assume that prolonged BAFF signalization may contribute to GC formation and/or lymphoma development in the disease. Finally, we discuss possibilities of novel treatments targeting the BAFF-system in SS.