Biological Treatment for Sjögren’s Syndrome

Abstract

The diffuse lymphocyte infiltration of target organs in Sjögren’s syndrome seems potentially amenable to therapies which might alter specific lymphocyte populations or their migration to tissues. Especially because this illness responds unsatisfactorily to conventional immunosuppression, efforts are underway to ameliorate disease using monoclonal antibodies, cytokines, and gene therapy. Promising data have been obtained using B-cell depletion with monoclonal antibodies, although further trials are necessary. Because B-cell homeostasis depends to a large degree on the cytokine BAFF/Blys, blocking of these molecules or their receptors may be a valuable approach in some patients. In Sjögren’s syndrome, the activation of interferon type I genes has opened the possibility that blocking antibodies to interferon-α or interferon-β may interrupt the disease process and reduce lymphocytic tissue infiltration. Monoclonal antibodies to adhesion molecules and other structures affecting lymphocyte homing may be particularly useful in this illness as well as antibodies to cytokines and their receptors, such as IL-6. Co-stimulation blockade using CTLA-4 is worthy of consideration for Sjögren’s syndrome treatment, in light of the important role for T cells in this illness. Finally, while far from clinical use, the delivery of cytokines such as IL-10 by viral vectors or other forms of gene therapy is also an appealing approach. The next few years should bear witness to important new, rational biological approaches to Sjögren’s syndrome which should increase our understanding of its basis and provide welcome relief for patients with severe illness.