Document Detail


Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals.
MedLine Citation:
PMID:  23379430     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have indicated phenotypical differences in glutamic acid decarboxylase 65 autoantibodies (GADA) found in type 1 diabetes (T1D) patients, individuals at risk of developing T1D and stiff-person syndrome (SPS) patients. In a Phase II trial using aluminium-formulated GAD(65) (GAD-alum) as an immunomodulator in T1D, several patients responded with high GADA titres after treatment, raising concerns as to whether GAD-alum could induce GADA with SPS-associated phenotypes. This study aimed to analyse GADA levels, immunoglobulin (Ig)G1-4 subclass frequencies, b78- and b96·11-defined epitope distribution and GAD(65) enzyme activity in sera from four cohorts with very high GADA titres: T1D patients (n = 7), GAD-alum-treated T1D patients (n = 9), T1D high-risk individuals (n = 6) and SPS patients (n = 12). SPS patients showed significantly higher GADA levels and inhibited the in-vitro GAD(65) enzyme activity more strongly compared to the other groups. A higher binding frequency to the b78-defined epitope was found in the SPS group compared to T1D and GAD-alum individuals, whereas no differences were detected for the b96·11-defined epitope. GADA IgG1-4 subclass levels did not differ between the groups, but SPS patients had higher IgG2 and lower IgG4 distribution more frequently. In conclusion, the in-vitro GADA phenotypes from SPS patients differed from the T1D- and high-risk groups, and GAD-alum treatment did not induce SPS-associated phenotypes. However, occasional overlap between the groups exists, and caution is indicated when drawing conclusions to health or disease status.
Authors:
M Chéramy; C S Hampe; J Ludvigsson; R Casas
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-05     Completed Date:  2013-04-02     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  247-54     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Alum Compounds / administration & dosage
Autoantibodies / blood,  immunology*
Diabetes Mellitus, Type 1 / blood,  drug therapy,  immunology*
Female
Glutamate Decarboxylase / administration & dosage,  immunology*,  therapeutic use
Humans
Immunoglobulin G / blood,  immunology
Male
Middle Aged
Phenotype
Stiff-Person Syndrome / etiology,  immunology
Chemical
Reg. No./Substance:
0/Alum Compounds; 0/Autoantibodies; 0/Immunoglobulin G; 10043-01-3/aluminum sulfate; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 2
Comments/Corrections

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