Immune Tolerance Strategies in Siblings with Infantile Pompe Disease-Advantages for a Preemptive Approach to High-Sustained Antibody Titers.


Journal Article

Enzyme replacement therapy (ERT) has led to a significant improvement in the clinical course of patients with infantile Pompe disease (IPD), an autosomal recessive glycogen storage disorder characterized by the deficiency in lysosomal acid α-glucosidase. A subset of IPD patients mount a substantial immune response to ERT developing high sustained anti-rhGAA IgG antibody titers (HSAT) leading to the ineffectiveness of this treatment. HSAT have been challenging to treat, although preemptive approaches have shown success in high-risk patients (those who are cross-reactive immunological material [CRIM]-negative). More recently, the addition of bortezomib, a proteasome inhibitor known to target plasma cells, to immunotherapy with rituximab, methotrexate, and intravenous immunoglobulin has shown success at significantly reducing the anti-rhGAA antibody titers in three patients with HSAT. In this report, we present the successful use of a bortezomib-based approach in a CRIM-positive IPD patient with HSAT and the use of a preemptive approach to prevent immunologic response in an affected younger sibling. We highlight the significant difference in clinical course between the two patients, particularly that a pre-emptive approach was simple and effective in preventing the development of high antibody titers in the younger sibling, thus supporting the role of immune tolerance induction (ITI) in the ERT-naïve high-risk setting.

Full Text

Duke Authors

Cited Authors

  • Stenger, EO; Kazi, Z; Lisi, E; Gambello, MJ; Kishnani, P

Published Date

  • September 1, 2015

Published In

Volume / Issue

  • 4 /

Start / End Page

  • 30 - 34

PubMed ID

  • 26167453

Pubmed Central ID

  • 26167453

International Standard Serial Number (ISSN)

  • 2214-4269

Digital Object Identifier (DOI)

  • 10.1016/j.ymgmr.2015.05.004


  • eng

Conference Location

  • United States