Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders

Shannon R. Hinson, A. Sebastian Lopez-Chiriboga, James Howard Bower, Joseph Y. Matsumoto, Anhar Hassan, Eati Basal, Vanda A Lennon, Sean J Pittock, Andrew B McKeon

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. Methods To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. Results GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum, but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). Conclusions GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. Classification of evidence This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

Original languageEnglish (US)
Article numbere438
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume5
Issue number2
DOIs
StatePublished - Mar 1 2018

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Stiff-Person Syndrome
Glycine Receptors
Antibodies
Myoclonus
Nervous System Diseases
Anxiety
Immunoglobulin G
Plasma Exchange
Delirium
Azathioprine
Neurologic Manifestations
Endocytosis
Serum
Immunotherapy
Medical Records
Healthy Volunteers
Adrenal Cortex Hormones
Extremities
Biomarkers
Maintenance

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders. / Hinson, Shannon R.; Lopez-Chiriboga, A. Sebastian; Bower, James Howard; Matsumoto, Joseph Y.; Hassan, Anhar; Basal, Eati; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew B.

In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 5, No. 2, e438, 01.03.2018.

Research output: Contribution to journalArticle

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title = "Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders",
abstract = "Background Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. Methods To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. Results GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5{\%}) and in 8 of 190 healthy subject sera (4{\%}) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum, but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100{\%} specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60{\%}) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89{\%}, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). Conclusions GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. Classification of evidence This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.",
author = "Hinson, {Shannon R.} and Lopez-Chiriboga, {A. Sebastian} and Bower, {James Howard} and Matsumoto, {Joseph Y.} and Anhar Hassan and Eati Basal and Lennon, {Vanda A} and Pittock, {Sean J} and McKeon, {Andrew B}",
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AU - Hinson, Shannon R.

AU - Lopez-Chiriboga, A. Sebastian

AU - Bower, James Howard

AU - Matsumoto, Joseph Y.

AU - Hassan, Anhar

AU - Basal, Eati

AU - Lennon, Vanda A

AU - Pittock, Sean J

AU - McKeon, Andrew B

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N2 - Background Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. Methods To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. Results GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum, but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). Conclusions GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. Classification of evidence This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

AB - Background Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. Methods To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. Results GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum, but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). Conclusions GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. Classification of evidence This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

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