Document Detail


Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: induction of humoral tolerance in seroconverted patients after repeat administration.
MedLine Citation:
PMID:  10068682     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alglucerase, a macrophage-targeted enzyme replacement therapy for Gaucher disease, has been successfully used for several years to improve clinical symptoms and reverse disease progression. As part of an immunosurveillance program, 1,122 Gaucher patients were monitored for antibody response to glucocerebrosidase, the active component of alglucerase. Seroconversion was detected in 142 patients (12.8%) by enzyme-linked immunosorbent assay (ELISA) and confirmed by radioimmunoprecipitation. The majority (75%) of the seroconverted population had no detectable levels of circulating inhibitory antibody as assessed by in vitro inhibition of enzymatic activity of the therapeutic molecule. Of the remaining patients with putative inhibitory antibodies, the majority had only low levels of serum inhibitory activity, which was transient. A very small number of patients were identified as developing true neutralizing antibodies, as defined by the development of antibodies that impacted clinical efficacy. Many of the patient antibody responses were also diminished with time. Eighty-two of the 142 seroconverted patients have stopped producing antibody to the molecule and appear tolerized. The mean time for humoral tolerization was 28 months from initiation of therapy. Of 64 seroconverted patients followed for at least 30 months of therapy, the tolerization rate was 93%. These results show that although 12.8% of the patients on therapy developed antibodies to the molecule, 90% of these patients became tolerized over time.
Authors:
M Rosenberg; W Kingma; M A Fitzpatrick; S M Richards
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Blood     Volume:  93     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-03-30     Completed Date:  1999-03-30     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2081-8     Citation Subset:  AIM; IM    
Affiliation:
Genzyme Corp, Framingham, MA 01701-9322, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / blood*
Enzyme-Linked Immunosorbent Assay
Gaucher Disease / drug therapy*,  immunology*
Glucosylceramidase / antagonists & inhibitors,  immunology*,  therapeutic use*
Humans
Immune Tolerance*
Immunoglobulin E / blood
Immunoglobulin G / blood
Kinetics
Monitoring, Immunologic*
Chemical
Reg. No./Substance:
0/Antibodies; 0/Immunoglobulin G; 37341-29-0/Immunoglobulin E; EC 3.2.1.-/alglucerase; EC 3.2.1.45/Glucosylceramidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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