DPPX potassium channel antibody: Frequency, clinical accompaniments, and outcomes in 20 patients

William Tobin, Vanda A Lennon, Lars Komorowski, Christian Probst, Stacey Lynn Clardy, Allen Jr. Aksamit, Juan Pablo Appendino, Claudia F Lucchinetti, Joseph Y. Matsumoto, Sean J Pittock, Paola Sandroni, Maja Tippmann-Peikert, Elaine C Wirrell, Andrew B McKeon

Research output: Contribution to journalArticle

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Abstract

Objective: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Methods: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Results: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: Amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. Conclusions: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

Original languageEnglish (US)
Pages (from-to)1797-1803
Number of pages7
JournalNeurology
Volume83
Issue number20
DOIs
StatePublished - Nov 1 2014

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Potassium Channels
Antibodies
Immunoglobulin G
Stiff-Person Syndrome
Nervous System Diseases
Immunotherapy
Brain Stem
Shal Potassium Channels
Autonomic Nervous System Diseases
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Primary Dysautonomias
Gastroparesis
Ocular Motility Disorders
Dysarthria
Abnormal Reflexes
Gastrin-Secreting Cells
Myoclonus
Gastrointestinal Neoplasms
Amnesia
1,3-dipropyl-8-phenylxanthine

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

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DPPX potassium channel antibody : Frequency, clinical accompaniments, and outcomes in 20 patients. / Tobin, William; Lennon, Vanda A; Komorowski, Lars; Probst, Christian; Clardy, Stacey Lynn; Aksamit, Allen Jr.; Appendino, Juan Pablo; Lucchinetti, Claudia F; Matsumoto, Joseph Y.; Pittock, Sean J; Sandroni, Paola; Tippmann-Peikert, Maja; Wirrell, Elaine C; McKeon, Andrew B.

In: Neurology, Vol. 83, No. 20, 01.11.2014, p. 1797-1803.

Research output: Contribution to journalArticle

Tobin, William ; Lennon, Vanda A ; Komorowski, Lars ; Probst, Christian ; Clardy, Stacey Lynn ; Aksamit, Allen Jr. ; Appendino, Juan Pablo ; Lucchinetti, Claudia F ; Matsumoto, Joseph Y. ; Pittock, Sean J ; Sandroni, Paola ; Tippmann-Peikert, Maja ; Wirrell, Elaine C ; McKeon, Andrew B. / DPPX potassium channel antibody : Frequency, clinical accompaniments, and outcomes in 20 patients. In: Neurology. 2014 ; Vol. 83, No. 20. pp. 1797-1803.
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abstract = "Objective: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Methods: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Results: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: Amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. Conclusions: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.",
author = "William Tobin and Lennon, {Vanda A} and Lars Komorowski and Christian Probst and Clardy, {Stacey Lynn} and Aksamit, {Allen Jr.} and Appendino, {Juan Pablo} and Lucchinetti, {Claudia F} and Matsumoto, {Joseph Y.} and Pittock, {Sean J} and Paola Sandroni and Maja Tippmann-Peikert and Wirrell, {Elaine C} and McKeon, {Andrew B}",
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T1 - DPPX potassium channel antibody

T2 - Frequency, clinical accompaniments, and outcomes in 20 patients

AU - Tobin, William

AU - Lennon, Vanda A

AU - Komorowski, Lars

AU - Probst, Christian

AU - Clardy, Stacey Lynn

AU - Aksamit, Allen Jr.

AU - Appendino, Juan Pablo

AU - Lucchinetti, Claudia F

AU - Matsumoto, Joseph Y.

AU - Pittock, Sean J

AU - Sandroni, Paola

AU - Tippmann-Peikert, Maja

AU - Wirrell, Elaine C

AU - McKeon, Andrew B

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Objective: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Methods: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Results: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: Amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. Conclusions: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

AB - Objective: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. Methods: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. Results: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: Amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. Conclusions: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

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