Engineered variants of human glutamic acid decarboxylase (GAD) and autoantibody epitope recognition.
Of the two homologous forms of glutamic acid decarboxylase, GAD65 and GAD67, only GAD65 is a common target of autoimmunity. Epitope profiles of autoantibodies to GAD65 (GADA) in 140 type 1 diabetes, adult-onset diabetes mellitus (AODM), and thyroid diseases (TD) were studied. Probes were GAD65, GAD65/67 hybrids (displaying separately GAD65 residues 1-95, 96-444, and 445-585), delta GAD65 (a truncated GAD65 spanning residues 69-585), and GAD67. delta GAD65 and GAD65 detected 137 and 125 positive patients, respectively. The hybrids reacted with 113 sera and in 3 cases disclosed cryptic epitopes. Eighteen patients reacted with GAD67, indicating GAD65-GAD67 cross-reactivity. Most patients recognized both middle and C-terminal epitopes, had low reactivity against N-terminal epitopes, and seldom displayed reactivity limited to the N or C terminus. Compared with type 1 and AODM, TD patients showed a greater prevalence of multiple reactivity and higher incidence of GAD67 positivity.
Primo
M E
ME
Cátedra de Inmunología, Facultad de Farmacia y Bioquimica, and IDEHU, CONICET-Universidad de Buenos Aires, 1026 Capital Federal, Argentina.
Anton
E A
EA
Villanueva
A L
AL
Poskus
E
E
Ermácora
M R
MR
D001323:Autoantibodies / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D015202:Protein Engineering
D001323:Autoantibodies; D000939:Epitopes; D005968:Glutamate Decarboxylase