Special Precautions/Comments:

Method: Enzyme Linked ImmunoSorbent assay (ELISA). Calibration: NIBSC 97/550. EQA scheme: UK NEQAS scheme for Diabetic Markers. IQC: Commercial preparation and kit controls.

Interferences: None known.

Additional Information:

Indication: Autoimmune Diabetes Mellitus and Stiff Person Syndrome (SPS

Background Information: Glutamic acid decarboxylase (GAD), which is involved in the formation of gamma-aminobutyric acid (GABA) from L-glutamic acid, exists as two different isoforms, GAD65 and GAD67. GAD65 is encoded by gene Gad 2 and GAD 67 by gene Gad 1. Both Gad 1 and Gad 2 are expressed in the brain with Gad 2 also being expressed in the pancreas. GAD antibodies directed against linear epitopes are associated with Stiff Persons Syndrome (GAD65 and GAD67 antibodies) whilst those recognising conformational epitopes are seen in insulin dependent diabetes (GAD65 antibodies). Antibodies to GAD65 and GAD67 are cross reactive. GAD65 antibodies are associated with autoimmune diabetes in the prediabetic stage and early diabetes. In the assessment of first degree relatives for autoimmune diabetes, positive results in more than one of the marker antibodies (GAD, Islet cell, IA-2 or insulin) can be associated with the onset of autoimmune diabetes [1]. GAD65 antibodies are seen in 70-80% of caucasians with newly diagnosed type 1 diabetes [1]. GAD65 antibodies are higher and more common in patients with other associated autoimmune disorders such as thyroiditis [1].

References: Nice guideline 15. Type 1 diabetes: diagnosis of type 1 diabetes in adults. 2004. Saiz A, Blanco Y, Sabater L. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008. 131:2556-2563. Skorstad G, et al. GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence. European Journal of Neurology. 2008. 15(9):973-980. Rakocevic G, et al. Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology. 2007. 68(14):1161. Pihoker C, et al. Autoantibodies in diabetes. Diabetes. 2005. 54(Suppl 2):S52-S61. [Ref 1] Chang T, Lang B. GAD antibodies in Stiff-Person Syndrome. Neurology. 2004. 63(11):1999-2000. Lohmann T, et al. Immune reactivity to glutamic acid decarboxylase 65 in stiff-man syndrome and type 1 diabetes mellitus. Lancet. 2000. 356:31-35

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