Characteristics of in-vitro phenotypes of glutamic acid decarboxylase 65 autoantibodies in high-titre individuals
Chéramy, Mikael Hampe, Christiane S. Ludvigsson, Johnny Casas, Rosaura
2013 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 171, no 3, 247-254Article in journal (Refereed) Published
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.
GAD65 immunotheraphy; GADA; stiff-person syndrome; type 1 diabetes
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84840DOI: 10.1111/cei.12026ISI: 000314655100003OAI: oai:DiVA.org:liu-84840DiVA: diva2:562436
The title of the article in manuscript form was "Characteristics of GAD65 autoantibodies (GADA) in high titer individuals".2012-10-242012-10-242013-03-14Bibliographically approved