The immune system in systemic lupus erythematosus is characterized by abnormal activation of various cell types, such as T and B lymphocytes, macrophages and dendritic cells and the production of autoantibodies against nuclear antigens. Until recently most of the pathogenic autoantibodies were thought to be IgG antibodies. We have recently shown that Lyn deficient mice develop a lupus nephritis-like disease which is mediated by basophils activated by IgE autoantibodies. Moreover, SLE patients also have elevated serum self reactive IgEs, and activated basophils that express the lymph node homing molecule CD62L and the MHC Class II molecule, HLA-DR; markers that are associated with increased disease activity. Follow up studies confirmed an association of IgE anti-dsDNA antibodies with active SLE using a SLEDAI score of 4 as a cutoff (unpublished). In addition, we have also observed a strong correlation of IgE dsDNA antibodies with hypocomplementemia strongly suggesting that these autoantibodies are serologic markers of immune activation in SLE. Based on these observations we propose that depleting IgE (including IgE autoantibodies) may lead to improvement in SLE by reducing IgE-induced basophil activation.