Immune tolerance induction to enzyme-replacement therapy by co-administration of short-term, low-dose methotrexate in a murine Pompe disease model
Open Access
- 16 February 2008
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 152 (1), 138-146
- https://doi.org/10.1111/j.1365-2249.2008.03602.x
Abstract
Summary: Clinical investigations of recombinant human acid α-glucosidase for the treatment of Pompe disease often reveal the appearance of therapy-specific antibodies. These antibodies could potentially interfere with recombinant human acid α-glucosidase efficacy and induce immunological consequences. Several immunosuppressive agents, including methotrexate, mycophenolate mofetil and cyclosporin A with azathioprine, were evaluated for their potential to induce immune tolerance to recombinant human acid α-glucosidase. Methotrexate was the only agent that reduced recombinant human acid α-glucosidase-specific antibody responses in acid α-glucosidase knock-out mice. A 3-week, low-dose methotrexate regimen controlled recombinant human acid α-glucosidase-specific antibody levels throughout 8 months of weekly recombinant human acid α-glucosidase treatment. The success of this methotrexate regimen appears to require methotrexate administration within the first 24 h of recombinant human acid α-glucosidase treatment. In an attempt to understand the benefit of methotrexate within the first day of recombinant human acid α-glucosidase administration, the immune response 24 h following intravenous recombinant human acid α-glucosidase treatment was investigated. A consistent expansion of peritoneal B1 B cells was observed. Control over this B1 B cell response may be part of the complex mechanism of action of methotrexate-induced immune tolerance.This publication has 41 references indexed in Scilit:
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