CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Kathryn L BerrierPriya S Kishnani

Abstract

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. 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). 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. Immunological responses are a significant risk in CN IPD; thus induction of immune tolerance in t...Continue Reading

References

Jan 9, 2009·The New England Journal of Medicine·Nancy J MendelsohnPriya S Kishnani
Mar 17, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Marc NicolinoPriya S Kishnani
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Jun 4, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Suhrad G BanugariaPriya S Kishnani
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Citations

Dec 23, 2015·Molecular Genetics and Metabolism Reports·Deeksha S BaliPriya S Kishnani
Aug 2, 2016·Nature Nanotechnology·Takashi K KishimotoRoberto A Maldonado
May 12, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Mrudu HerbertPriya S Kishnani
Sep 15, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Zoheb B KaziPriya S Kishnani
Sep 7, 2017·Acta Neuropathologica Communications·J HordeauxM-A Colle
Apr 11, 2018·BMJ Paediatrics Open·Narcisse ElengaJean-François Benoist
Oct 6, 2020·Frontiers in Immunology·Punita GuptaPriya S Kishnani
Nov 21, 2017·The Cochrane Database of Systematic Reviews·Min ChenShuyan Quan
Jan 19, 2021·EMBO Molecular Medicine·Giancarlo ParentiAndrea Ballabio
Jan 1, 2018·Molecular Genetics and Metabolism·Ankit K DesaiPriya S Kishnani
May 31, 2020·The Journal of Pediatrics·Amy G FeldmanCara L Mack
Aug 24, 2021·Cardiology in the Young·Barry J ByrneUNKNOWN Pompe ADVANCE Study Consortium
Nov 23, 2017·Pediatrics·David F KronnUNKNOWN Pompe Disease Newborn Screening Working Group

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Methods Mentioned

BETA
enzyme-linked immunosorbent assays

Clinical Trials Mentioned

NCT01665326

Software Mentioned

STATA

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