The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders

Journal of Inherited Metabolic Disease
A BroomfieldBrian W Bigger


In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved in the development of anti-drug antibodies and the current therapies used in their treatment. Given the current understanding of the adaptive immune response, it focuses particularly on T cell dependent mechanisms and the paradigm of using lymphocytic negative selection as a predictor of antibody formation. This concept originally postulated in the 1970s, stipulated that the genotypically determined lack of production or production of a variant protein determines an individual's lymphocytic repertoire. This in turn is the key factor in determining the potential severity of an individual's immunological response to ERT. It also highlights the need for immunological assay standardization particularly those looking at describing the degree of functional impact, robust biochemical or clinical endpoints and detailed patient subgroup identification if the true evaluations of impact are to be realised.


Feb 1, 1982·Diabetologia·S WalfordW G Reeves
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·R M ShullE F Neufeld
Apr 1, 1996·Current Opinion in Biotechnology·N Jenkins
Jul 6, 2000·Immunopharmacology·S Matsuda, S Koyasu
Jun 21, 2001·JAMA : the Journal of the American Medical Association·R SchiffmannR O Brady
Mar 5, 2003·Annual Review of Immunology·Ralph M SteinmanMichel C Nussenzweig
Mar 27, 2003·Nature Reviews. Immunology·Jeffrey A Bluestone, Abul K Abbas
Apr 17, 2003·The Journal of Clinical Investigation·Imke TiedeMarkus F Neurath
Jan 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·E KakkisM Passage
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Massimo C FantiniMarkus F Neurath
Sep 3, 2004·Nature Reviews. Immunology·Bruno Kyewski, Jens Derbinski
Sep 30, 2004·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Mar 15, 2006·Annals of Neurology·Tokiko FukudaNina Raben
Oct 10, 2006·The AAPS Journal·Amy S Rosenberg
Nov 25, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·J Oldenburg, A Pavlova
Dec 23, 2006·Molecular Genetics and Metabolism·Joseph MuenzerAlan Kimura
Sep 6, 2007·Endocrine Reviews·S Edwin FinebergAlan S Krasner
Oct 30, 2007·Trends in Immunology·Anne S De Groot, David W Scott
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hualin LiCatarina E Hioe
Sep 19, 2008·Immunity·Yasmine Belkaid, Guillaume Oldenhove
Nov 11, 2008·Journal of Pharmaceutical and Biomedical Analysis·Gopi ShankarEugen Koren
Nov 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Robert M AnthonyJeffrey V Ravetch
Jan 9, 2009·The New England Journal of Medicine·Nancy J MendelsohnPriya S Kishnani
Feb 10, 2009·Current Drug Targets·Masanori Onda

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