title: The role of antibodies in enzyme treatments and therapeutic strategies.
abstract: Substitution of the defective lysosomal enzyme in lysosomal storage disorders (LSDs) often elicits antibody formation towards the infused protein. Aside from Gaucher disease, antibodies often lead to infusion associated reactions and a reduced biochemical response. In Pompe disease, antibody titer is predictive of clinical outcome, but this is less apparent in other LSDs and warrants further study. Few laboratories are capable of enzyme-antibody determination: often physicians need to rely on the enzyme manufacturer for analysis. Currently, laboratories employ different antibody assays which hamper comparisons between cohorts or treatment regimens. Assay standardisation, including measurement of antibody-related enzyme inhibition, is therefore urgently needed. Successful immunomodulation has been reported in Pompe and in Gaucher disease, with variable success. Immunomodulation regimens that contain temporary depletion of B-cells (anti-CD20) are most used. Bone marrow transplantation in MPS-I results in disappearance of antibodies. No other clinical studies have been conducted in humans with immunomodulation in other LSDs.
authors.affiliation: Stem Cell & Neurotherapies Laboratory, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: brian.bigger@manchester.ac.uk.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Bigger
authors.affiliation: Department of Clinical Haematology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. Electronic address: muhammad.saif@cmft.nhs.uk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Saif
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: g.e.linthorst@amc.uva.nl.
authors.forename: Gabor E
authors.initials: GE
authors.lastname: Linthorst
mesh_terms: D000906:Antibodies / Q000276:immunology; D056947:Enzyme Replacement Therapy; D057487:Enzyme Therapy; D004798:Enzymes / Q000276:immunology; D000795:Fabry Disease / Q000188:drug therapy / Q000276:immunology; D005776:Gaucher Disease / Q000188:drug therapy / Q000276:immunology; D005087:Glucan 1,4-alpha-Glucosidase / Q000276:immunology / Q000627:therapeutic use; D005962:Glucosylceramidase / Q000276:immunology / Q000627:therapeutic use; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D016464:Lysosomal Storage Diseases / Q000188:drug therapy* / Q000276:immunology; D000519:alpha-Galactosidase / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D004798:Enzymes; D007518:Isoantibodies; D000519:alpha-Galactosidase; D005087:Glucan 1,4-alpha-Glucosidase; D005962:Glucosylceramidase
keywords: antibodies; biomarker; lysosomal storage diseases enzyme replacement therapy; response