Purpose of review
This review provides an update on the specific, strong association between dysregulated production of the cytokine B-cell activation factor and Sjögren's syndrome, and offers new perspectives on potential pathogenic mechanisms.
Excess B-cell activation factor in mice triggers Sjögren's syndrome-like symptoms, and elevated serum B-cell activation factor in humans correlates with Sjögren's syndrome. B-cell activation factor is produced locally by activated monocytes, T cells and dendritic cells, and by epithelial cells and infiltrating B cells. Moreover, recent data in humans suggest that the innate immune system plays a role as an initiator of immune disorders in inflamed tissues.
Recent data have demonstrated the critical role of B-cell activation factor and B cells in the pathogenesis of Sjögren's syndrome, and its association with B lymphomas. Moreover, B-cell depleting treatments have confirmed the critical role of B cells in Sjögren's syndrome. Excess B-cell activation factor possibly corrupts B-cell tolerance and allows the emergence of self-reactive B cells that efficiently present antigen to T cells. In addition, B-cell activation factor may stimulate T-cell independent activation of B cells via Toll-like receptors; this recently identified mechanism could also play a separate, detrimental role in autoimmunity.