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

Publication date: Available online 31 January 2019

Source: Clinical Immunology

Author(s): A.S. De Groot, Z.B. Kazi, R.F. Martin, F.E. Terry, A.K. Desai, W.D. Martin, P.S. Kishnani

Abstract

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.

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