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Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals.

Abstract：

: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.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Chéramy M,Hampe CS,Ludvigsson J,Casas R

doi

10.1111/cei.12026

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

247-54

issue

3

eissn

0009-9104

issn

1365-2249

journal_volume

171

pub_type

杂志文章

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