Engineered variants of human glutamic acid decarboxylase (GAD) and autoantibody epitope recognition

Clin Immunol. 2003 Jul;108(1):38-45. doi: 10.1016/s1521-6616(03)00061-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Epitopes / immunology*
  • Glutamate Decarboxylase / genetics*
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Protein Engineering*


  • Autoantibodies
  • Epitopes
  • Glutamate Decarboxylase