 Introduction Systemic lupus erythematosus SLE affects predominantly young women with childbearing potential 20-40 years and inflammation can occur in virtually every organ, including kidneys, lungs, heart or brain. The disease course in SLE patients is typically characterized by frequent flares, requiring immunosuppressive treatment. Current, evidence-based treatment modalities for SLE consist of immunosuppressive treatment with high dose corticosteroids, cyclophosphamide or mycophenolic mycophenolate acid, that non-specifically target the immune system to reduce inflammation. Side-effects of these treatment strategies are opportunistic infections in the short term and risk for malignancy and cardiovascular disease in the long-term. Treating SLE patients with biologicals is an attractive alternative because biologicals specifically target the immune system by blocking cytokines or deplete one specific cell population, thereby reducing the risk for infections or malignancies as compared to conventional immunosuppressants. Furthermore, the scarce treatment options underscore the need to exploit new therapeutic possibilities for SLE patients who frequently experience a flare of the disease. These considerations led to the present study involving a proof-of-concept study in refractory SLE patients to assess the immunological consequences of a combination treatment with rituximab anti-CD20 and belimumab anti-BAFF. 