Autoantibody aids identification of hyperexcitability disorders

Researchers have found that testing for a glycine receptor autoantibody aids the identification of a broad spectrum of autoimmune brainstem/spinal cord hyperexcitability disorders.

Detection of the autoantibody, namely glycine receptor a1-immunoglobulin G (GlyRa1-IgG), may also be predictive for response to immunotherapy in patients who have such disorders, report Josep Dalmau (University of Pennsylvania, Philadelphia, USA) and colleagues in the Archives of Neurology.

Furthermore, the diagnostic use of the autoantibody may extend beyond the spinal cord and brainstem to the glycinergic visual system.

In a review of medical records available for 81 patients with classic stiff-man syndrome (SMS) and phenotypically similar disorders, GlyRa1-IgG was detected in 10 (12%) individuals. Four of them had classic SMS (which principally affects the lumbar spine and proximal lower extremities), five had variant SMS (limited to the axis or extremities, eg, stiff-leg syndrome), and one had progressive encephalomyelitis with rigidity and myoclonous phenotype (PERM).

In an accompanying editorial, David Pleasure (University of California, Sacramento, USA) comments: "Although there have been prior case reports of patients with GlyRa1 autoantibody-positive PERM, the present series is the first to document GlyRa1 autoantibodies in stiff-leg syndrome and stiff-person syndrome."

Three other autoantibodies have been associated with SMS disorders to date, the most prevalent of which is an IgG that binds to glutamic acid decarboxylase 65 (GAD65), an intracellular enzyme that synthesizes ?-aminobutryic acid (GABA) in neurons.

However, in the current study, GlyRa1-IgG was detected in six (10%) of 60 individuals with samples positive for GAD65-IgG as well as in four (19%) of 21 individuals with samples that were negative for GAD65-IgG.

Among patients with the SMS phenotype who had immunotherapy data available, substantial responses to treatment were more frequent in individuals who were seropositive for GlyRa1-IgG than in those who were seronegative, at 86% versus 28%.

"Thus, in clinical practice, serologic tests for GlyRa1-IgG complement tests for GAD65-IgG… in aiding identification of autoimmune brainstem/spinal cord hyperexcitability disorders that are potentially immunotherapy responsive," writes the team.

The researchers also found that, among 100 control individuals who either had other autoimmune neurologic disorders (n=80) or were healthy (n=20), only one individual (who had neuromyelitis optica) was positive for GlyRa1-IgG.

This finding suggests that the spectrum of GlyRa1-IgG receptor autoimmunity extends beyond the spinal cord and brainstem, say the researchers. "Of pertinence, glycine and ?-aminobutyric acid are the major inhibitory neurotransmitters of human retina."

Systematic investigation of the neuroopthalmic spectrum of glycine receptor autoimmunity is needed," they conclude.

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Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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