Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome
| Autor: | Anil K. Chauhan, Alan P. Knutsen, Miguel A. Guzman, Clifford J. Bellone, Shunji Tomatsu, Adriana M. Montaño, Luis A. Barrera, Angela C. Sosa, Qi Gan, Eric Armbrecht, Barbara Kariuki |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Administration
Oral CHO Cells Immunoglobulin E Mice Immune system Cricetulus Splenocyte Immune Tolerance Cytotoxic T cell Medicine Animals Humans Enzyme Replacement Therapy Adverse effect Mice Knockout biology business.industry Sulfatase Mucopolysaccharidosis IV General Medicine Enzyme replacement therapy Chondroitinsulfatases Desensitization Immunologic Immunoglobulin G Immunology biology.protein Cytokines Cytokine secretion business Peptides Research Article |
| Zdroj: | J Clin Invest |
| Popis: | Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects. Here we show development of tolerance in Morquio A mice via oral delivery of peptide or GALNS for 10 days prior to ERT. Our results show that using an immunodominant peptide (I10) or the complete GALNS enzyme to orally induce tolerance to GALNS prior to ERT resulted in several improvements to ERT in mice: (a) decreased splenocyte proliferation after in vitro GALNS stimulation, (b) modulation of the cytokine secretion profile, (c) decrease in GALNS-specific IgG or IgE in plasma, (d) decreased GAG storage in liver, and (e) fewer circulating immune complexes in plasma. This model could be extrapolated to other lysosomal storage disorders in which immune response hinders ERT. |
| Databáze: | OpenAIRE |
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