The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis
Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann KU, Wiethe C, Winkler T, Kalden J, Manz RA, Voll RE (2008)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2008
Journal
Book Volume: 14
Pages Range: 748-755
Journal Issue: 7
DOI: 10.1038/nm1763
Abstract
Autoantibody-mediated diseases like myasthenia gravis, autoimmune hemolytic anemia and systemic lupus erythematosus represent a therapeutic challenge. In particular, long-lived plasma cells producing autoantibodies resist current therapeutic and experimental approaches. Recently, we showed that the sensitivity of myeloma cells toward proteasome inhibitors directly correlates with their immunoglobulin synthesis rates. Therefore, we hypothesized that normal plasma cells are also hypersensitive to proteasome inhibition owing to their extremely high amount of protein biosynthesis. Here we show that the proteasome inhibitor bortezomib, which is approved for the treatment of multiple myeloma, eliminates both short- and long-lived plasma cells by activation of the terminal unfolded protein response. Treatment with bortezomib depleted plasma cells producing antibodies to double-stranded DNA, eliminated autoantibody production, ameliorated glomerulonephritis and prolonged survival of two mouse strains with lupus-like disease, NZB/W F1 and MRL/lpr mice. Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases. © 2008 Nature Publishing Group.
Authors with CRIS profile
Kerstin Ute Amann
Department of Nephropathology
Thomas Winkler
Professur für Genetik
Joachim Kalden
Medizinische Fakultät
Involved external institutions
Germany (DE)How to cite
APA:
Neubert, K., Meister, S., Moser, K., Weisel, F., Maseda, D., Amann, K.U.,... Voll, R.E. (2008). The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nature Medicine, 14(7), 748-755. https://dx.doi.org/10.1038/nm1763
MLA:
Neubert, Kirsten, et al. "The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis." Nature Medicine 14.7 (2008): 748-755.
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