CRIM-negative Infantile Pompe Disease: Characterization of Immune Responses in Patients Treated with ERT Monotherapy

Overview

Journal Genet Med

Publisher Elsevier

Specialty Genetics

Date 2015 Mar 6

PMID 25741864

Citations 37

Authors

Kathryn L Berrier

Zoheb B Kazi

Sean N Prater

Deeksha S Bali

Jennifer Goldstein

Mihaela C Stefanescu

Catherine W Rehder

Eleanor G Botha

Carolyn Ellaway

Kaustuv Bhattacharya

Anna Tylki-Szymanska

Nesrin Karabul

Amy S Rosenberg

Priya S Kishnani

Affiliations

Soon will be listed here.

Abstract

Purpose: Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) prolongs survival in infantile Pompe disease (IPD). However, the majority of cross-reactive immunologic material (CRIM)-negative (CN) patients have immune responses with significant clinical decline despite continued ERT. We aimed to characterize immune responses in CN patients with IPD receiving ERT monotherapy.

Methods: A chart review identified 20 CN patients with IPD treated with ERT monotherapy for ≥6 months. Patients were stratified by anti-rhGAA antibody titers: high sustained antibody titers (HSAT; ≥51,200) at least twice; low titers (LT; <6,400) throughout treatment; or sustained intermediate titers (SIT; 6,400-25,600).

Results: Despite early initiation of treatment, the majority (85%) of CN patients developed significant antibody titers, most with HSAT associated with invasive ventilation and death. Nearly all patients with HSAT had at least one nonsense GAA mutation, whereas the LT group exclusively carried splice-site or frameshift mutations. Only one patient in the HSAT group is currently alive after successful immune modulation in the entrenched setting.

Conclusion: Immunological responses are a significant risk in CN IPD; thus induction of immune tolerance in the naive setting should strongly be considered. Further exploration of factors influencing immune responses is required, particularly with the advent of newborn screening for Pompe disease.

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