Screening for antibodies against the GAD antigen is used to investigate patients with neurological diseases such as stiff-person syndrome (or stiff-man syndrome), limbic encephalitis, epilepsy, and cerebral ataxia. Screening for antibodies against GAD (and more specifically to GAD65) is also performed in patients with type 1 diabetes (insulin-dependent diabetes mellitus).
There are two isoforms of the GAD enzyme with a molecular weight of 65 kDa and 67 kDa. GAD-65 is mainly expressed in the pancreas, whereas both GAD-65 and GAD-67 are expressed in the CNS.
IgG antibodies against GAD occur in the serum of patients with type 1 diabetes in approximately 70-80% of newly diagnosed individuals. Concomitant presence of antibodies against pancreatic islet cells, beta-cell antigen 2 (IA-2), insulin (IAA), and zinc transporter 8 enhances the diagnosis. Antibodies can be detected before clinical evidence of type 1 diabetes mellitus. Slightly elevated values may also occur in other autoimmune endocrine disorders, in particular autoimmune thyroiditis.
Anti-GAD antibodies also occur in 60% of patients with stiff-person syndrome and have been observed in both serum and cerebrospinal fluid (CSF). Anti-GAD antibodies can also occur in limbic encephalitis, epilepsy, and cerebral ataxia. The association of antibodies against GAD with cancer is unusual but has been reported in various forms of cancer (breast cancer, small cell lung, endocrine tumors). Patients with neurological symptoms often have much higher anti-GAD antibody titers than patients with type 1 diabetes mellitus.
The antigen for the assay of antibodies against GAD comprises a mixture of the isoforms of the enzyme (GAD-65 and GAD-67), while the antigen for the assay of antibodies against GAD-65 used to test type 1 diabetes comprises only the GAD-65 isoform.
See also: GAD65 Antibodies