B lymphocytestimulator (BLyS) is a vital B cell survivalfactor. Overexpressionof BLyS in mice may lead to systemic lupus erythematosus (SLE)-like disease, and treatment of bona fide SLE mice with BLyS antagonists ameliorates disease progression and enhances survival. BLyS overexpression is common in human SLE, and results from a phase I clinical trial with a BLyS antagonistin human SLE have shown the antagonist to be biologicallyactive and safe. These features collectivelypoint to BLyS as an attractive therapeutic target in human disease.
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