Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report.

Autor: Kim S; University of Minnesota, College of Pharmacy, 420 Delaware St SE, MMC 391, Minneapolis, MN 55455-0341, USA., Whitley CB; University of Minnesota, Department of Experimental and Clinical Pharmacology, College of Pharmacy, 420 Delaware St SE, MMC 446, Minneapolis, MN 55455-0341, USA; Advanced Therapies Program, University of Minnesota and Fairview Hospitals, Minneapolis, MN 55454, USA; University of Minnesota, Department of Pediatrics, Medical School, 420 Delaware St SE, MMC 446, Minneapolis, MN 55455-0341, USA., Jarnes Utz JR; University of Minnesota, Department of Experimental and Clinical Pharmacology, College of Pharmacy, 420 Delaware St SE, MMC 446, Minneapolis, MN 55455-0341, USA; Advanced Therapies Program, University of Minnesota and Fairview Hospitals, Minneapolis, MN 55454, USA; University of Minnesota, 420 Delaware St SE; MMC 391, Minneapolis, MN 55455-0341, USA; University of Minnesota, Department of Pediatrics, 420 Delaware St SE, Minneapolis, MN 55454-1450, USA. Electronic address: utzx0002@umn.edu.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2017 Sep; Vol. 122 (1-2), pp. 92-99. Date of Electronic Publication: 2017 Jun 03.
DOI: 10.1016/j.ymgme.2017.06.001
Abstrakt: Introduction: Antibodies to intravenous idursulfase enzyme replacement therapy (ERT) for patients with Hunter syndrome (mucopolysaccharidosis type II, MPS II) can have a harmful clinical impact, including both increasing risk of infusion reactions and inhibiting therapeutic activity. Thus, failure to monitor anti-idursulfase antibodies and neutralizing antibodies, and delays in reporting results, may postpone critical clinical decisions.
Hypothesis: Urinary glycosaminoglycan (GAG) levels may be used as a biomarker for anti-idursulfase antibodies and neutralizing antibodies to improve timeliness in monitoring and managing ERT.
Methods: This is a case report describing a patient with MPS II with high levels of neutralizing antibodies and worsened clinical status who was treated for five years with a non-immunosuppressive and non-cytotoxic immune tolerance (NICIT) regimen, consisting of intravenous immune globulin and frequent infusions of idursulfase. Neutralizing antibodies and total anti-idursulfase antibodies were measured by two different methods, the direct 1,9-dimethylmethylene blue (DMB) assay and cetylpyridinium chloride carbazole-borate (CPC) assay.
Results: Neutralizing antibodies, measured as percent inhibition of enzyme activity and also by total neutralizing antibody titer, were correlated with quantitative urinary GAG measured by DMB assay (p=0.026, p=0.0067), and quantitative urinary GAG by CPC assay with percent inhibition of enzyme activity by neutralizing antibodies (p=0.0475). The NICIT regimen showed a sustained immune tolerance after five years and was well-tolerated.
Conclusions: Urinary GAG, measured by DMB assay, may be a biomarker for anti-idursulfase neutralizing antibodies and is useful for managing immune tolerance regimens for patients with MPS II who have high levels of anti-idursulfase neutralizing antibodies. This study highlights the importance of regular and frequent monitoring of urinary GAG in patients with MPS II who are receiving ERT. The NICIT regimen, with less drug toxicities, may be preferred in patients with MPS who have a high risk of infections and whose disease progresses less rapidly than some other lysosomal storage diseases, such as infantile Pompe disease.
(Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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