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Title: Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis
Authors: Gomez, Alejandro M.
Vrolix, Kathleen
Martinez-Martinez, Pilar
Molenaar, Peter C.
Phernambucq, Marko
van der Esch, Eline
Duimel, Hans
Verheyen, Fons
Voll, Reinhard E.
Manz, Rudolf A.
Losen, Mario
Issue Date: 2011
Source: JOURNAL OF IMMUNOLOGY, 186(4). p. 2503-2513
Abstract: Bortezomib, an inhibitor of proteasomes, has been reported to reduce autoantibody titers and to improve clinical condition in mice suffering from lupus-like disease. Bortezomib depletes both short- and long-lived plasma cells; the latter normally survive the standard immunosuppressant treatments targeting T and B cells. These findings encouraged us to test whether bortezomib is effective for alleviating the symptoms in the experimental autoimmune myasthenia gravis (EAMG) model for myasthenia gravis, a disease that is characterized by autoantibodies against the acetylcholine receptor (AChR) of skeletal muscle. Lewis rats were immunized with saline (control, n = 36) or Torpedo AChR (EAMG, n = 54) in CFA in the first week of an experimental period of 8 wk. After immunization, rats received twice a week s.c. injections of bortezomib (0.2 mg/kg in saline) or saline injections. Bortezomib induced apoptosis in bone marrow cells and reduced the amount of plasma cells in the bone marrow by up to 81%. In the EAMG animals, bortezomib efficiently reduced the rise of anti-AChR autoantibody titers, prevented ultrastructural damage of the postsynaptic membrane, improved neuromuscular transmission, and decreased myasthenic symptoms. This study thus underscores the potential of the therapeutic use of proteasome inhibitors to target plasma cells in Ab-mediated autoimmune diseases. The Journal of Immunology, 2011, 186: 2503-2513.
Notes: [Gomez, Alejandro M.; Vrolix, Kathleen; Martinez-Martinez, Pilar; Molenaar, Peter C.; Phernambucq, Marko; van der Esch, Eline; De Baets, Marc H.; Losen, Mario] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Neurosci, Neuroimmunol Group, NL-6200 MD Maastricht, Netherlands. [van der Esch, Eline; Duimel, Hans; Verheyen, Fons] Maastricht Univ, Dept Mol Cell Biol, Electron Microscopy Unit, NL-6200 MD Maastricht, Netherlands. [Voll, Reinhard E.] Univ Hosp Erlangen, Nikolaus Fiebiger Ctr Mol Med, Dept Internal Med 3, Erlangen, Germany. [Manz, Rudolf A.] Univ Lubeck, Inst Syst Inflammat Res, Lubeck, Germany. [De Baets, Marc H.] Hasselt Univ, Biomed Res Inst, Neuroimmunol Group, Diepenbeek, Belgium.
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ISSN: 0022-1767
e-ISSN: 1550-6606
DOI: 10.4049/jimmunol.1002539
ISI #: 000286882700070
Category: A1
Type: Journal Contribution
Validations: ecoom 2012
Appears in Collections:Research publications

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