title: 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.
authors: Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. mikael.cheramy@liu.se
authors: M
authors: M
authors: Chéramy
authors: C S
authors: CS
authors: Hampe
authors: J
authors: J
authors: Ludvigsson
authors: R
authors: R
authors: Casas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000534:Alum Compounds / Q000008:administration & dosage; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016750:Stiff-Person Syndrome / Q000209:etiology / Q000276:immunology
chemical_list: D000534:Alum Compounds; D001323:Autoantibodies; D007074:Immunoglobulin G; C041524:aluminum sulfate; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
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