| First Author | Joseph A | Year | 2008 |
| Journal | Clin Exp Immunol | Volume | 152 |
| Issue | 1 | Pages | 138-46 |
| PubMed ID | 18307520 | Mgi Jnum | J:133581 |
| Mgi Id | MGI:3778864 | Doi | 10.1111/j.1365-2249.2008.03602.x |
| Citation | Joseph A, et al. (2008) Immune tolerance induction to enzyme-replacement therapy by co-administration of short-term, low-dose methotrexate in a murine Pompe disease model. Clin Exp Immunol 152(1):138-46 |
| abstractText | Clinical investigations of recombinant human acid alpha-glucosidase for the treatment of Pompe disease often reveal the appearance of therapy-specific antibodies. These antibodies could potentially interfere with recombinant human acid alpha-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 alpha-glucosidase. Methotrexate was the only agent that reduced recombinant human acid alpha-glucosidase-specific antibody responses in acid alpha-glucosidase knock-out mice. A 3-week, low-dose methotrexate regimen controlled recombinant human acid alpha-glucosidase-specific antibody levels throughout 8 months of weekly recombinant human acid alpha-glucosidase treatment. The success of this methotrexate regimen appears to require methotrexate administration within the first 24 h of recombinant human acid alpha-glucosidase treatment. In an attempt to understand the benefit of methotrexate within the first day of recombinant human acid alpha-glucosidase administration, the immune response 24 h following intravenous recombinant human acid alpha-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. |
