Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice.
Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). A single dose of the anti-BlyS antibody temporarily lowered the percentage of B cells and IgG antibody titer against recombinant human GLA. Administration of a low maintenance dose of the anti-BlyS antibody suppressed the B cell population and immunotolerance was induced in 20% of mice, but antibody formation could not be prevented. We then increased the maintenance dose of the anti-BlyS antibody and immunotolerance was induced in 50% of mice. Therapeutic enzyme distribution and clearance of GL-3 were also enhanced by a high maintenance dose of the anti-BlyS antibody.
Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
Yohei
Y
Sato
Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
Hiroyuki
H
Ida
Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: tohashi@jikei.ac.jp.
Toya
T
Ohashi
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000188:drug therapy* / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007074:Immunoglobulin G / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology* / Q000627:therapeutic use; D014281:Trihexosylceramides / Q000378:metabolism; D000519:alpha-Galactosidase / Q000276:immunology* / Q000627:therapeutic use
D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D014281:Trihexosylceramides; C018549:globotriaosylceramide; C511911:belimumab; D000519:alpha-Galactosidase
Anti-BlyS antibody; Enzyme replacement therapy; Fabry disease; Immune tolerance induction; Neutralizing antibody