Dataset Information

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI.

ABSTRACT: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic, and multisystem lysosomal storage disease. Enzyme replacement therapy (ERT) with the recombinant human arylsulfatase B enzyme (galsulfase [Naglazyme]) is recommended as first-line therapy. It is generally reported as safe and well tolerated. Frequently observed mild to moderate infusion-related reactions which can be easily handled by reducing or interrupting the infusion and/or administering additional antihistamines, antipyretics, and corticosteroids are mostly mediated by non-IgE mechanisms. Here we report two children with MPS VI who experienced IgE-mediated reactions with galsulfase at the second year of the therapy. One child had anaphylaxis and the other had urticarial eruptions. They could receive ERT after successful rapid desensitization. To our knowledge, this is the second report on galsulfase allergy with IgE-mediated reaction. It is important to recognize IgE-mediated reactions since they can be life-threatening and do not respond to the standard therapies. We recommend allergy skin tests in the evaluation of infusion-related reactions unresponsive to standard therapies, so that continuation of ERT will be feasible after successful desensitization.

SUBMITTER: Tamay Z

PROVIDER: S-EPMC5110439 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI.

Tamay Zeynep Z Gokcay Gulden G Dilek Fatih F Balci Mehmet Cihan MC Ozceker Deniz D Demirkol Mubeccel M Guler Nermin N

JIMD reports 20160308

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic, and multisystem lysosomal storage disease. Enzyme replacement therapy (ERT) with the recombinant human arylsulfatase B enzyme (galsulfase [Naglazyme]) is recommended as first-line therapy. It is generally reported as safe and well tolerated. Frequently observed mild to moderate infusion-related reactions which can be easily handled by reducing or interrupting the infusion and/or administering additional antihistamines, antipyretic ...[more]

PMID: 26951141

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Project description:BACKGROUND: Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome; MPS VI) is an autosomal recessive lysosomal storage disorder in which deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B; ARSB) leads to the storage of glycosaminoglycans (GAGs) in connective tissue. The genotype-phenotype correlation has been addressed in several publications but the picture is not complete. Since 2007, enzyme-replacement therapy (ERT) has been available for patients with MPS VI in the Netherlands. The purpose of our study was to learn more about the genotype-phenotype correlations in MPS VI and the antibody response to ERT with galsulfase (recombinant human arylsulfatase B). METHODS: We identified ARSB mutations in 12 patients and used site-directed mutagenesis to study their effect. Antibody levels to galsulfase were measured using ELISA and a semi-quantitative immunoprecipitation method. We assessed the in vitro inhibitory effect of antibodies on galsulfase uptake and their effect on clinical outcome. RESULTS: Five patients had a rapidly progressive phenotype and seven a slowly progressive phenotype. In total 9 pathogenic mutations were identified including 4 novel mutations (N301K, V332G, A237D, and c.1142?+?2 T?>?C) together composing 8 pathogenic genotypes. Most mutations appeared not to affect the synthesis of ARSB (66 kD precursor), but to hamper its maturation (43 kD ARSB). Disease severity was correlated with urinary GAG excretion. All patients developed antibodies to galsulfase within 26 weeks of treatment. It was demonstrated that these antibodies can inhibit the uptake of galsulfase in vitro. CONCLUSIONS: The clinical phenotypes and the observed defects in the biosynthesis of ARSB show that some of the mutations that we identified are clearly more severe than others. Patients receiving galsulfase as enzyme-replacement therapy can develop antibodies towards the therapeutic protein. Though most titers are modest, they can exceed a level at which they potentially affect the clinical outcome of enzyme-replacement therapy.

Dataset Information

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI.

Publications

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI.

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