1. L’antagoniste se lie à Blys
Les antagonistes de Blys favorisent l’apoptose des lymphocytes B autoréactifs
Maladie auto-immune
L’antagoniste se lie à Blys
Le lymphocyte B survit
Excess BLyS promotes the survival of autoreactive B cells otherwise destined for apoptosis; BLys antagonists allow apoptosis to proceed.
BLyS antagonists block BLyS from binding to its receptor; such blocking prevents NF-B signaling and upregulation of anti-apoptotic genes. Without these “survival” proteins, the B cell undergoes apoptosis.1,2
Because BLyS receptors are not expressed at every stage of B-cell development, BLyS-targeted therapy is restricted to early-stage B cells in the periphery without affecting late-stage compartments, such as memory or bone marrow plasma cells, and without compromising immunity.3
By reducing BLyS levels to “normal” or below a threshold critical for an autoimmune response, antagonists may potentially ameliorate SLE.4
References
Kanakaraj P et al. BLyS binds to B cells with high affinity and induces activation of the transcription factors Nf-kappa-β and ELF-1. Cytokine. 2001;13:25-31.
Do RK et al. Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response. J Exp Med ;192:
Cancro MP et al. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest. 2009;119:
Stohl W. BlySfulness does not equal blissfulness in systemic lupus erythematosus: a therapeutic role for BLyS antagonists. Curr Dir Autoimmun. 2005;8:
Le lymphocyte B meurt
BLyS
BR3 or TACI or BCMA
Antagoniste de Blys 1
Cancro MP et al. J Clin Invest. 2009;119: