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Clearing of globotriaosylceramide from endothelial vessels of ocular conjunctiva in patients with Fabry disease treated with agalsidase alfa
Author(s) -
Rozenfeld P.,
Ebner R.,
Croxatto O.,
Fossati C.
Publication year - 2006
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.2006.tb02403.x
Subject(s) - globotriaosylceramide , fabry disease , enzyme replacement therapy , medicine , conjunctiva , alpha galactosidase , immunofluorescence , pathology , antibody , disease , immunology
: Fabry disease is an X‐linked inborn metabolic error caused by a deficiency of lysosomal α‐galactosidase A. Globotriaosylceramide (Gb 3 ) accumulates in lysosomes of various cells. At the moment, enzyme replacement therapy (ERT) is the only available specific treatment for patients with Fabry disease. Enzyme infusions reduce the Gb 3 content of plasma, urine sediment and tissue. In a previous study, we reported the development of a method to specifically detect Gb 3 deposits by immunofluorescence in conjunctival biopsies. Aim : The aim of this work is to evaluate the clearance of Gb 3 in cells from the conjunctiva in patients with Fabry disease treated with agalsidase alfa. Methods : Conjunctival biopsies were obtained from three hemizygous and two heterozygous patients, before and after 6 months of treatment with agalsidase alfa. The specimens were processed for direct immunofluorescence using an anti‐Gb 3 monoclonal antibody and light microscopy using a mouse polyclonal antiserum specific for α‐galactosidase A. Results : Positive immunofluorescence was not observed in cells from the blood vessels of patients with Fabry disease after 6 months of treatment, as compared with the specimens before the treatment, which were positive. We detected Gb 3 in stromal/macrophage cells that were distal from the blood vessels where the enzyme was circulating. Specific staining for α‐galactosidase A revealed the presence of this protein in the tissue of patients after ERT, but not before. Conclusion : Agalsidase alfa eliminated Gb 3 deposits from the cells of blood vessel walls in patients with Fabry disease after 6 months of treatment. The deposits in stromal cells were not removed, probably because the enzyme must diffuse into the tissue to reach these cells and/or because of the short length of therapy. This method may be useful to evaluate the effectiveness of ERT.