Persistence of high sustained antibodies to enzyme replacement therapy despite extensive immunomodulatory therapy in an infant with Pompe disease: need for agents to target antibody-secreting plasma cells.

Journal Article (Journal Article)

With the advent of enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA, Myozyme®) for Pompe disease, the clinical course of the disease has changed. We have previously described the poor outcome in cross reactive immunologic material (CRIM)-negative and high-titer CRIM-positive (HTCP) patients secondary to high sustained antibody titers (HSAT) which effectively neutralize ERT efficacy. Various immunomodulation strategies are being explored to diminish the immune response to ERT. However, once HSAT are formed, tolerization therapy has uniformly failed to lower antibody titers. Here we describe a case in which immunomodulation over a prolonged period of 28 months with cyclophosphamide, intravenous immunoglobulin, plasmapheresis, increased doses of rhGAA and rituximab failed to lower antibody titers and resulted in continued clinical decline in an infantile Pompe disease patient treated with ERT. Thus, it appears that the failure to target the antibody-secreting plasma cells responsible for HSAT led to a failure of tolerance induction. This is the first report using this combination of agents over a very extensive period of time with no success.

Full Text

Duke Authors

Cited Authors

  • Banugaria, SG; Patel, TT; Mackey, J; Das, S; Amalfitano, A; Rosenberg, AS; Charrow, J; Chen, Y-T; Kishnani, PS

Published Date

  • April 2012

Published In

Volume / Issue

  • 105 / 4

Start / End Page

  • 677 - 680

PubMed ID

  • 22365055

Pubmed Central ID

  • PMC3711263

Electronic International Standard Serial Number (EISSN)

  • 1096-7206

Digital Object Identifier (DOI)

  • 10.1016/j.ymgme.2012.01.019


  • eng

Conference Location

  • United States