​Sjögren syndrome is a chronic autoimmune disease. It is characterized by lymphocytic infiltration of the salivary and lacrimal glands, resulting in buccal and ocular dryness, and multiple systemic complications associated with auto-antibody production, including an increased risk of B-cell lymphoma. 

About twenty years ago, Prof. Xavier Mariette's team showed the role of a cytokine, specifically B-cell activating factor (BAFF; a member of the TNF family), in B lymphocyte hyperactivation in Sjögren syndrome. Since then, the team has helped show the interest of antibodies targeted against CD20 (a B-lymphocyte surface protein) for the treatment of several autoimmune diseases. 

However, further work found that anti-CD20 treatments lead to an increase in BAFF levels, which, in turn, can lead to the stimulation of new autoreactive B lymphocytes, which, coming full circle, can reduce the efficacy of anti-CD20 therapies. This conundrum gave birth to the idea of associating two antibodies, one against CD20 and the other against BAFF, for the treatment of Sjögren syndrome.

In a recent work, Mariette's autoimmune team (UMR-S 1184 CEA/Inserm/UPSaclay/Kremlin Bicêtre) did just that, successfully deploying the strategy in patients with severe systemic complications secondary to Sjögren syndrome. These patients were treated with an association of two already market-approved monoclonal antibodies: rituximab, an anti-CD20 used in inflammatory arthritis; and belimumab, an anti-BAFF for the treatment of systemic lupus. 

As compared to each used alone, the association of the two antibodies improved therapeutic responses and especially reduced the amount of tissular B lymphocytes present in the salivary glands, one of the primary tissues affected by autoimmune infiltration in Sjögren syndrome.