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Original Contribution |

Glycine Receptor Autoimmune Spectrum With Stiff-Man Syndrome Phenotype

Andrew McKeon, MD; Eugenia Martinez-Hernandez, MD; Eric Lancaster, MD, PhD; Joseph Y. Matsumoto, MD; Robert J. Harvey, BSc, PhD; Kathleen M. McEvoy, MD, PhD; Sean J. Pittock, MD; Vanda A. Lennon, MD, PhD; Josep Dalmau, MD, PhD
JAMA Neurol. 2013;70(1):44-50. doi:10.1001/jamaneurol.2013.574.
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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.

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Grahic Jump Location

Figure 1. Graph showing that 81 patients with stiff-man syndrome (SMS) phenotype (classic, variant, progressive encephalomyelitis with rigidity and myoclonus [PERM], and hyperekplexia) were tested for glycine receptor α1 (GlyRα1)–IgG.

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Grahic Jump Location

Figure 2. Glycine receptor α1 (GlyRα1)–IgG demonstrated in HEK293 cells expressing the human GlyRα1 subunit. The reactivity of serum from 2 representative patients with HEK293 cells expressing the human GlyRα1 subunit is shown in panels A and D. G, Serum from a control patient lacks reactivity with transfected cells. Panels B, E, and H show the reactivity with a commercial GlyRα1 monoclonal antibody. The immunostaining colocalizes with that of patient antibodies (C and F, but not I). Scale bar = 20 μm.

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