A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins

Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 165(2016) vom: 16. Apr., Seite 55-9
1. Verfasser: Rosenberg, A S (VerfasserIn)
Weitere Verfasser: Pariser, A R, Diamond, B, Yao, L, Turka, L A, Lacana, E, Kishnani, P S
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Review Autoantibodies Enzyme replacement therapy Immune tolerance Plasma cells Antineoplastic Agents Bortezomib 69G8BD63PP
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520 |a Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology 
650 4 |a Journal Article 
650 4 |a Review 
650 4 |a Autoantibodies 
650 4 |a Enzyme replacement therapy 
650 4 |a Immune tolerance 
650 4 |a Plasma cells 
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650 7 |a Bortezomib  |2 NLM 
650 7 |a 69G8BD63PP  |2 NLM 
700 1 |a Pariser, A R  |e verfasserin  |4 aut 
700 1 |a Diamond, B  |e verfasserin  |4 aut 
700 1 |a Yao, L  |e verfasserin  |4 aut 
700 1 |a Turka, L A  |e verfasserin  |4 aut 
700 1 |a Lacana, E  |e verfasserin  |4 aut 
700 1 |a Kishnani, P S  |e verfasserin  |4 aut 
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856 4 0 |u http://dx.doi.org/10.1016/j.clim.2016.02.009  |3 Volltext 
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