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

Clin Immunol

Cátedra de Inmunología, Facultad de Farmacia y Bioquimica, and IDEHU, CONICET-Universidad de Buenos Aires, 1026 Capital Federal, Argentina.

Published: July 2003

AI Article Synopsis

  • Of the two forms of glutamic acid decarboxylase, only GAD65 is commonly targeted by autoimmune responses, particularly in type 1 diabetes and thyroid diseases.
  • A study analyzed autoantibody profiles against GAD65 and its hybrids and found that GAD65 and delta GAD65 identified a large number of positive patients, while hybrids revealed hidden epitopes.
  • Patients primarily showed immune responses to middle and C-terminal regions of GAD65, with thyroid disease patients exhibiting more diverse reactivity and a higher occurrence of GAD67 positivity compared to type 1 diabetes and adult-onset diabetes cases.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/s1521-6616(03)00061-5DOI Listing

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