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

Clin Immunol. 2019 Mar:200:66-70. doi: 10.1016/j.clim.2019.01.009. Epub 2019 Jan 31.


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.

Keywords: ADA; Enzyme replacement therapy; Immunogenicity; Immunoinformatics; Pompe Disease.

MeSH terms

  • Antibodies / immunology*
  • Computer Simulation
  • Cross Reactions / immunology
  • Enzyme Replacement Therapy*
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology
  • Glycogen Storage Disease Type II / drug therapy
  • Glycogen Storage Disease Type II / genetics*
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Immune Tolerance / immunology
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use
  • Infant
  • Methotrexate / therapeutic use
  • Recombinant Proteins
  • Risk Assessment
  • Rituximab / therapeutic use
  • alpha-Glucosidases / genetics*
  • alpha-Glucosidases / immunology*
  • alpha-Glucosidases / therapeutic use


  • Antibodies
  • Epitopes, T-Lymphocyte
  • HLA-DRB1 Chains
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Recombinant Proteins
  • Rituximab
  • GAA protein, human
  • alpha-Glucosidases
  • Methotrexate