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Author:
Chéramy, Mikael (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Hampe, Christiane S. (Department of Medicine, University of Washington, Seattle, WA, USA)
Ludvigsson, Johnny (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences) (Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping)
Casas, Rosaura (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Title:
Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals
Department:
Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping
Linköping University, Faculty of Health Sciences
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics
Publication type:
Article in journal (Refereed)
Language:
English
Publisher: John Wiley & Sons
Status:
Published
In:
Clinical and Experimental Immunology(ISSN 0009-9104)(EISSN 1365-2249)
Volume:
171
Issue:
3
Pages:
247-254
Year of publ.:
2013
URI:
urn:nbn:se:liu:diva-84840
Permanent link:
http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-84840
ISI:
000314655100003
Subject category:
Medical and Health Sciences
Keywords(en) :
GAD65 immunotheraphy; GADA; stiff-person syndrome; type 1 diabetes
Abstract(en) :

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 GAD65 (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 GAD65 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 GAD65 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.

Note:

The title of the article in manuscript form was "Characteristics of GAD65 autoantibodies (GADA) in high titer individuals".

Available from:
2012-10-24
Created:
2012-10-24
Last updated:
2013-03-14
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