Fabry disease, enzyme replacement therapy and the significance of antibody responses.
Fabry disease is an X-linked disorder caused by a deficiency of α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide in tissues throughout the body. Cardiac, renal and neurological manifestations are common and life expectancy is significantly reduced relative to the general population. Management of Fabry disease involves the administration of intravenous enzyme replacement therapy (ERT). Two forms - agalsidase alfa and agalsidase beta - have been licensed in certain jurisdictions and are generally well tolerated; however, some patients develop antibodies to the infused enzyme, which may impair the efficacy and safety of treatment. Agalsidase alfa and agalsidase beta are produced in different systems; this leads to certain differences in post-translational modification that may affect immunogenicity. Immunoglobulin (Ig) G antibodies have frequently been reported in patients with Fabry disease receiving ERT; IgG responses are reported in a greater proportion of patients receiving agalsidase beta than in patients receiving agalsidase alfa. IgE antibodies are less common than IgG antibodies, and have not been observed in patients receiving agalsidase alfa. However, these data are difficult to interpret due to methodological differences in the assessment of seropositivity, and in the doses of enzyme used. The clinical impact of the development of IgG antibodies to ERT in patients with Fabry disease remains unclear, due to lack of data and to the marked heterogeneity of patients both in terms of disease manifestations and response to therapy. Further studies that examine the development of antibodies in patients with Fabry disease and the potential impact of such antibodies on the outcome of ERT are necessary.
Department of Medicine, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK. patrick.deegan@addenbrookes.nhs.uk
Patrick B
PB
Deegan
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D056947:Enzyme Replacement Therapy / Q000379:methods; D000795:Fabry Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000276:immunology / Q000627:therapeutic use*; D011994:Recombinant Proteins; D000519:alpha-Galactosidase / Q000276:immunology / Q000627:therapeutic use*
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta