Developments in the diagnostic potential of antibodies to glutamic acid decarboxylase

Abstract EN

Autoantibodies to glutamic acid decarboxylase (GAD-Abs) occur in type I diabetes, polyendocrine autoimmunity (PE) and stiff-man syndrome (SMS), and are diagnostic and predictive markers.

We investigated GAD-Abs in patients being assessed for SMS, comparing ELISAs employing GAD- enriched rat brain preparation with an immunoprecipitation assay using radio¬labelled human GAD.

An ELISA in which GAD was captured with an N- terminal-specific monoclonal antibody (mAb) showed similar sensitivity and specificity to the immunoprecipitation assay, whereas lower sensitivity and specificity were shown by an ELISA employing a capture mAb (GAD-6) spe¬cific for the C-terminal region of GAD, and by an ELISA in which the rat brain preparation was coated directly onto the plate.

The direct ELISA de¬tected additional antibodies in paraneoplastic SMS patients (probably anti-amphiphysin).

We investigated autoantibodies to a subregion of GAD in PE by determining the ability of serum antibodies to inhibit the binding of GAD-6 mAb to GAD in direct ELISA.

Patients were heterogeneous in the occurrence of these antibodies.

There was no significant difference between PE patients with or without diabetes, although the highest levels of inhibition were given by sera from non-diabetic patients.

Differential expression of subsets of GAD- Abs may be of predictive value.