Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype

JAMA Neurol. 2013 Jan;70(1):44-50. doi: 10.1001/jamaneurol.2013.574.

Abstract

Objectives: To determine whether glycine receptor α1 subunit-specific autoantibodies (GlyRα1-IgG) occur in a broader spectrum of brainstem and spinal hyperexcitability disorders than the progressive encephalomyelitis with rigidity and myoclonus phenotype recognized to date, and to ascertain disease specificity.

Design: Retrospective, case-control study.

Settings: Mayo Clinic, Rochester, Minnesota, and University of Barcelona, Spain.

Patients: Eighty-one patients with stiff-man syndrome phenotype, 80 neurologic control subjects, and 20 healthy control subjects.

Intervention: Glycine receptor α1-transfected cells to test serum or cerebrospinal fluid from cases and control subjects.

Main outcome measures: Frequency of GlyRα1-IgG positivity among stiff-man syndrome phenotype cases and control subjects. Comparison of GlyRα1-IgG seropositive and seronegative cases.

Results: Seropositive cases (12% of cases) included 9 with stiff-man syndrome (4 classic; 5 variant; 66% were glutamic acid decarboxylase 65-IgG positive) and 1 with progressive encephalomyelitis with rigidity and myoclonus. Immunotherapy responses were noted more frequently in GlyRα1-IgG-positive cases (6 of 7 improved) than in seronegative cases (7 of 25 improved; P= .02). The single seropositive control patient had steroid-responsive vision loss and optic atrophy with inflammatory cerebrospinal fluid.

Conclusions: Glycine receptor α1-IgG aids identification of autoimmune brainstem/spinal cord hyperexcitability disorders and may extend to the glycinergic visual system.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Autoantibodies / biosynthesis*
  • Autoantibodies / genetics
  • Brain Stem / immunology
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Case-Control Studies
  • Child, Preschool
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Middle Aged
  • Phenotype*
  • Protein Subunits / genetics
  • Protein Subunits / immunology
  • Receptors, Glycine / blood*
  • Receptors, Glycine / genetics
  • Receptors, Glycine / immunology
  • Retrospective Studies
  • Stiff-Person Syndrome / genetics
  • Stiff-Person Syndrome / immunology*

Substances

  • Autoantibodies
  • Protein Subunits
  • Receptors, Glycine