BlySfulness does not equal blissfulness in systemic lupus erythematosus: a therapeutic role for BLyS antagonists.
B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Constitutive overexpression of BLyS in mice can lead to systemic lupus erythematosus (SLE)-like disease. Mice which naturally develop SLE harbor elevated circulating levels of BLyS, and treatment of these mice with BLyS antagonists ameliorates disease progression and enhances survival. In human SLE, BLyS overexpression is also common. Results from a phase-I clinical trial in human SLE with a neutralizing anti-BLyS monoclonal antibody have shown the antagonist to be biologically active and safe. These features collectively point to BLyS and/or its receptors as attractive therapeutic targets in human SLE.
Stohl
William
W
Division of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. stohl@usc.edu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009500:Neutralization Tests; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D000069283:Rituximab; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000276:immunology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab