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

M. E. PRIMO,; E. A. ANTON; A. L. VILLANUEVA; E. POSKUS; M. R. ERMÁCORA

CLINICAL IMMUNOLOGY

Ed. Elsevier

Lugar: USA; Año: 2003 vol. 18 p. 38 - 45

1521-6616

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), dGAD65 (a truncated GAD65 spanning residues 69‑585), and GAD67. dGAD65 was more sensitive than GAD65 (137 vs. 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.