Potential Use of anti-IgE in the Treatment of Lupus Nephritis

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.