title: Autoantibodies to glutamic acid decarboxylase (GAD) detected by an immuno-trapping enzyme activity assay: relation to insulin-dependent diabetes mellitus and islet cell antibodies.
abstract: It has recently been proposed that the islet 64,000 Mr protein autoantigen (64K) of insulin-dependent diabetes mellitus (IDDM) is glutamic acid decarboxylase (GAD). We evaluated, by means of a newly developed immunotrapping enzyme activity assay (ITEAA), the prevalence of circulating GAD-autoantibodies (Ab) in a large population of IDDM patients (n = 168), blood donors (n = 87) and non-diabetic autoimmune patients (n = 40). The latter two groups were used as controls. Overall, GAD-Ab were found in 22% of IDDM patients, but in none of the two control groups (P = 0.007). These specificities were invariably associated with islet cell antibodies (ICA) (31.6% in IDDM with ICA vs 0 in IDDM without ICA, P = 0.0001), and this prevalence was higher in sera with high titer ICA (54.5% in IDDM with ICA greater than 80 JDF-units vs 22.6% of IDDM with ICA 5-80 JDF units; P = 0.002). Moreover, GAD-Ab were associated with the female sex (P = 0.002) and the concomitant presence of thyroid and/or gastric antibodies (P = 0.002). No correlation was observed between GAD-Ab and age of the patients, duration of IDDM, or associated non-organ specific antibodies. Our study indicates that GAD-Ab measured by ITEAA are: (1) detected in a proportion of IDDM patients; (2) strongly associated with ICA; (3) preferentially found in IDDM female patients with autoimmune polyendocrine serology; and (4) detected with lower frequency than that reported for 64K-Ab in IDDM.
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, University of Milan, Italy.
authors.forename: G V
authors.initials: GV
authors.lastname: Martino
authors.forename: M L
authors.initials: ML
authors.lastname: Tappaz
authors.forename: S
authors.initials: S
authors.lastname: Braghi
authors.forename: N
authors.initials: N
authors.lastname: Dozio
authors.forename: N
authors.initials: N
authors.lastname: Canal
authors.forename: G
authors.initials: G
authors.lastname: Pozza
authors.forename: G F
authors.initials: GF
authors.lastname: Bottazzo
authors.forename: L M
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: E
authors.initials: E
authors.lastname: Bosi
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology; D010295:Parietal Cells, Gastric / Q000276:immunology; D012737:Sex Factors; D013954:Thyroglobulin / Q000276:immunology
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody; C056626:thyroid microsomal antibodies; D013954:Thyroglobulin; D005968:Glutamate Decarboxylase