HLA- and genotype-based risk assessment model to identify infantile onset pompe disease patients at high-risk of developing significant anti-drug antibodies (ADA).

Journal Article (Journal Article)

In Pompe disease, anti-drug antibodies (ADA) to acid alpha-glucosidase (GAA) enzyme replacement therapy contribute to early mortality. Assessing individual risk for ADA development is notoriously difficult in (CRIM-positive) patients expressing endogenous GAA. The individualized T cell epitope measure (iTEM) scoring method predicts patient-specific risk of developing ADA against therapeutic recombinant human GAA (rhGAA) using individualized HLA-binding predictions and GAA genotype. CRIM-negative patients were six times more likely to develop high ADA titers than CRIM-positive patients in this retrospective study, whereas patients with high GAA-iTEM scores were 50 times more likely to develop high ADA titers than patients with low GAA-iTEM scores. This approach identifies high-risk IOPD patients requiring immune tolerance induction therapy to prevent significant ADA response to rhGAA leading to a poor clinical outcome and can assess ADA risk in patients receiving replacement therapy for other enzyme or blood factor deficiency disorders.

Full Text

Duke Authors

Cited Authors

  • De Groot, AS; Kazi, ZB; Martin, RF; Terry, FE; Desai, AK; Martin, WD; Kishnani, PS

Published Date

  • March 2019

Published In

Volume / Issue

  • 200 /

Start / End Page

  • 66 - 70

PubMed ID

  • 30711607

Pubmed Central ID

  • PMC6554735

Electronic International Standard Serial Number (EISSN)

  • 1521-7035

Digital Object Identifier (DOI)

  • 10.1016/j.clim.2019.01.009


  • eng

Conference Location

  • United States