The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis

Journal article
(Original article)


Publication Details

Author(s): Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann KU, Wiethe C, Winkler T, Kalden J, Manz RA, Voll RE
Journal: Nature Medicine
Publication year: 2008
Volume: 14
Journal issue: 7
Pages range: 748-755
ISSN: 1078-8956


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.



FAU Authors / FAU Editors

Amann, Kerstin Ute Prof. Dr.
Nephropathologische Abteilung im Pathologischen Institut
Kalden, Joachim Prof. Dr.
Medizinische Fakultät
Winkler, Thomas Prof. Dr.
Professur für Genetik


External institutions with authors

Deutsches Rheuma-Forschungszentrum (DRFZ)


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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Last updated on 2018-19-12 at 20:51