Journal of Inherited Metabolic Disease

, Volume 39, Issue 4, pp 499–512 | Cite as

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

  • A. Broomfield
  • S. A. Jones
  • S. M. Hughes
  • B. W. Bigger
SSIEM 2015


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.


Enzyme Replacement Therapy Fabry Disease Pompe Disease Peripheral Tolerance Agalsidase Beta 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with ethics guidelines

Conflict of interest

Alexander Broomfield funding for travel and consultancy from Genzyme Corporation UK (A Sanofi company) and travel grants from Shire UK and Biomarin Corporations.

Simon Jones has received Consultancy, research grants and speaking Honoraria for Genzyme Corporation UK (A Sanofi company), Biomarin, Ultragenyx, Alexion and Shire.

Brian Bigger has received grant funding for research from Shire UK Corporation.

Stephen Hughes declares no conflict of interest.

Informed consent

Not applicable as literature review.

Animal rights

This article does not contain any studies with animals performed by the authors.


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Copyright information

© SSIEM 2016

Authors and Affiliations

  • A. Broomfield
    • 1
  • S. A. Jones
    • 1
  • S. M. Hughes
    • 2
  • B. W. Bigger
    • 3
  1. 1.Willink Biochemical genetics unit, Manchester center for genomic medicine, St Mary’s HospitalCentral Manchester Foundation TrustManchesterUK
  2. 2.Department of Immunology, Royal Manchester children’s HospitalCentral Manchester Foundation TrustManchesterUK
  3. 3.Stem Cell & Neurotherapies Laboratory, Faculty of Medical and Human SciencesUniversity of ManchesterManchesterUK

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