Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease characterized by a significant morbidity and mortality related to both disease evolution as well as therapeutic side effects. At least half of SLE patients develop lupus nephritis.
The inventors have used a Lyn -/- mouse model that develops an autoimmune disease exhibiting some features of human SLE. Using this model the inventors identified basophils and self-reactive IgEs as important components in the development of autoantibody-mediated kidney disease. The inventors found that depletion of basophils or the absence of IgE causes a considerable reduction in autoantibody production and preserves kidney function in the Lyn -/- mice. The inventors' work demonstrates that IgE immune complexes can activate basophils and that removal of self-reactive IgEs that form functional circulating immune complexes prevents kidney disease. Further, the inventors have shown that basophils are contributors to the production of the self-reactive antibodies that cause lupus-like nephritis in the Lyn -/- mice. Accordingly, reducing circulating IgE levels or reducing basophil activation may be of therapeutic benefit.
Current treatment of lupus has not advanced for many years. This finding is of importance for its potential in advancing treatment of the disease.