Glutamic Acid Decarboxylase (GAD65) Antibody Assay, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Glutamic acid decarboxylase (GAD) is a neuronal enzyme involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). Antibodies directed against the 65-kd isoform of GAD (GAD65) are seen in a variety of autoimmune neurologic disorders including stiff-man (Moersch-Woltman) syndrome, autoimmune cerebellitis, brain stem encephalitis, seizure disorders, neuromyelitis optica and other myelopathies, myasthenia gravis, Lambert-Eaton syndrome, and dysautonomia.
GAD65 antibody is also the major pancreatic islet antibody and an important serological marker of predisposition to type 1 diabetes. GAD65 autoantibody also serves as a marker of predisposition to other autoimmune disease that occur with type 1 diabetes, including thyroid disease (eg, thyrotoxicosis, Graves' disease, Hashimoto's thyroiditis, hypothyroidism), pernicious anemia, premature ovarian failure, Addison's disease, (idiopathic adrenocortical failure) and vitiligo.
Assessing susceptibility to autoimmune (type 1, insulin-dependent) diabetes mellitus and related endocrine disorders (eg, thyroiditis and pernicious anemia). Titers generally < or = 0.02 nmol/L. A second islet cell antibody, IA-2, is more predictive for development of type 1 diabetes, but less frequent than GAD65 Ab amongst diabetic patients. Insulin autoantibodies also serve as a marker of susceptibility to type 1 diabetes.
Distinguishing between patients with type 1 and type 2 diabetes. Assays for IA-2, insulin, gastric parietal cell, thyroglobulin, and thyroid peroxidase antibodies, complement GAD65 antibody in this context. Titers generally < or = 0.02 nmol/L.
Confirming a diagnosis of stiff-man syndrome, autoimmune encephalitis, cerebellitis, brain stem encephalitis, myelitis. Titers generally > or = 0.03 nmol/L.
Confirming susceptibility to organ-specific neurological disorders (eg, myasthenia gravis, Lambert-Eaton syndrome). Titers generally < or = 0.02 nmol/L.
High titers (> or = 0.02 nmol/L) are found in classic stiff-man syndrome (93% positive) and in related autoimmune neurologic disorders (eg, acquired cerebellar ataxia, some acquired nonparaneoplastic encephalomyelopathies).
Diabetic patients with polyendocrine disorders also generally have GAD65 antibody values > or =0.02 nmol/L.
Values in patients who have type 1 diabetes without a polyendocrine or autoimmune neurologic syndrome are usually < or =0.02 nmol/L. Low titers (0.03-19.9 nmol/L) are detectable in the serum of approximately 80% of type 1 diabetic patients. Conversely, low titers are detectable in the serum of <5% of type 2 diabetic patients.
Low titers are found in approximately 25% of patients with myasthenia gravis, Lambert-Eaton syndrome, and rarer autoimmune neurological disorders. Eight percent of healthy Olmsted County residents over age 50 have low positive values. These are not false positive; the antibodies are inhibited by unlabelled GAD65 antigen and are accompanied in at least 50% of cases by related organ-specific autoantibodies.
Values > or =0.03 nmol/L are consistent with susceptibility to autoimmune (type 1) diabetes and related endocrine disorders (thyroiditis and pernicious anemia).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Antibodies specific for glutamic acid decarboxylase (GAD65) account for most, but not all, antibodies detected in the islet cell antibody test. IA-2 (a protein tyrosine kinase-like protein) insulin and zinc transporter-8 antibodies are complementary islet cell antibodies.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held one week and assayed if sufficiently decayed, or canceled if radioactivity remains.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =0.02 nmol/L
Reference values apply to all ages.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Walikonis JE, Lennon VA: Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc 1998 December;73(12):1161-1166
2. Kawasaki E, Yu L, Gianani R, et al: Evaluation of islet cell antigen (ICA) 512/IA-2 autoantibody radioassays using overlapping ICA512/IA-2 constructs. J Clin Endocrinol Metab 1997 February;82(2):375-380
3. Saiz A, Arpa J, Sagasta A, et al: Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus and polyendocrine autoimmunity. Neurology 1997 October;49(4):1026-1030
4. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc 2006;81:1207-1214