The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders
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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.
KeywordsEnzyme Replacement Therapy Fabry Disease Pompe Disease Peripheral Tolerance Agalsidase Beta
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.
Not applicable as literature review.
This article does not contain any studies with animals performed by the authors.
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