GlyR¶

Glycine receptor¶

Other names¶

GlyRA1

Description¶

The Anti-GlyR antibody is of the IgG1 or IgG3 isotype directed against the glycine receptor in the CNS. It is most often associated with stiff person spectrum disorders or brain and spinal disorders however it has also been seen in movement disorders, autoimmune epilepsy, and in patients with persistent visual disturbances.

May be found alongside other autoantibodies in 46%, most commonly anti-GAD antibodies. Malignancy is present in <10% of cases and is most often thymoma or Hodgkin's lymphoma.

CBA is the available test and it is recommended that paired serum and CSF samples are sent for analysis.

Mechanism of action¶

Glycine receptors are ligand gated chloride ion channels which are expressed throughout the CNS. The alpha 1 subunit is highly expressed in the brainstem, spinal cord, thalamus, hypothalamus, and colliculus.

Anti-Glycine receptor antibodies impair the ability of the receptor to facilitate glycinergic inhibitory transmission. An ex vivo model has demonstrated very fast effect on the glycinergic current compared to other autoantibodies and this occurred independent of the antibodies' ability to crosslink. This may suggest a direct antagonistic effect on the receptor in some patients. If confirmed this would require an alternate treatment strategy focusing on blocking antibody binding or removing the pathogenic autoantibody rather than reducing inflammatory effects of autoantibodies (such as the action of complement).

Associated clinical features¶

1. Ptosis, diplopia, nystagmus, slow/jerky movements
2. Often temporal lobe seizures

Associated neoplasia¶

<10% associated with malignancy, usually malignant thymoma and hodgkin lymphoma

Laboratory method¶

CBA expressing alpha 1 subunit of glycine receptor although subsequent CBA have used alpha 2 and 3 subunits which have found that the autoantibody often has affinity for a common epitope.

Imunoprecipitation in initial paper for quantification

Notes of performance characteristics¶

• 12-15% of patients with classic SPS and high titre {>>(>20,000 units)<<} anti-GAD antibodies will have concomitant anti-GlyR antibodies.
• 10% of patients with anti-GAD antibodies may have concomitant anti-GlyR antibodies.
• There is no correlation between anti-GAD titres and anti-GlyR titres.
• CSF more sensitive than serum. Patients with positive serum and CSF will not have clinically different disease to those with CSF positivity alone.
• Recommended to pair serum and CSF samples.
• While CSF titres are generally lower than serum titres of the antibody there is intrathecal synthesis in many patients.

Grade¶

Next steps¶