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Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome

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Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome. / Scharf, Madeleine; Miske, Ramona; Heidenreich, Fedor; Giess, Ralf; Landwehr, Peter; Blöcker, Inga-Madeleine; Begemann, Nora; Denno, Yvonne; Tiede, Stephan; Dähnrich, Cornelia; Schlumberger, Wolfgang; Unger, Mandy; Teegen, Bianca; Stöcker, Winfried; Probst, Christian; Komorowski, Lars.

In: NEUROLOGY, Vol. 84, No. 16, 21.04.2015, p. 1673-9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Scharf, M, Miske, R, Heidenreich, F, Giess, R, Landwehr, P, Blöcker, I-M, Begemann, N, Denno, Y, Tiede, S, Dähnrich, C, Schlumberger, W, Unger, M, Teegen, B, Stöcker, W, Probst, C & Komorowski, L 2015, 'Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome', NEUROLOGY, vol. 84, no. 16, pp. 1673-9. https://doi.org/10.1212/WNL.0000000000001493

APA

Scharf, M., Miske, R., Heidenreich, F., Giess, R., Landwehr, P., Blöcker, I-M., Begemann, N., Denno, Y., Tiede, S., Dähnrich, C., Schlumberger, W., Unger, M., Teegen, B., Stöcker, W., Probst, C., & Komorowski, L. (2015). Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome. NEUROLOGY, 84(16), 1673-9. https://doi.org/10.1212/WNL.0000000000001493

Vancouver

Scharf M, Miske R, Heidenreich F, Giess R, Landwehr P, Blöcker I-M et al. Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome. NEUROLOGY. 2015 Apr 21;84(16):1673-9. https://doi.org/10.1212/WNL.0000000000001493

Bibtex

@article{1bbc8dd76b5f476eaabf5aafe3935e7e,
title = "Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome",
abstract = "OBJECTIVES: To identify an autoreactivity in a 66-year-old woman who presented with combined brainstem and cerebellar syndrome including vertical gaze palsy, severe progressive ataxia, and spastic tetraparesis, an acute deterioration of vision, dysarthria, and dysphagia with concurrent diagnosis of a colon adenocarcinoma.METHODS: Patient's serum and CSF underwent comprehensive autoantibody screening by indirect immunofluorescence assay and immunoblot. For autoantigen purification, a histo-immunoprecipitation technique was developed followed by mass spectrometrical analysis. Recombinant candidate antigens were expressed in HEK293 and used to verify the identification.RESULTS: Indirect immunofluorescence assay screening revealed strong immunoglobulin G reactivity with neural tissues in serum and CSF, but not with a panel of 28 recombinantly expressed established neural autoantigens. The hitherto unknown target antigen was identified as the neuronal Na(+)/K(+) ATPase. Epitope mapping and competitive inhibition experiments showed that the autoantibodies were directed against the membrane-spanning alpha 3 subunit (ATP1A3) of the enzyme but did not bind to extracellular epitopes. Immunohistochemical analysis revealed overexpression of this subunit in the patient's tumor.CONCLUSIONS: We describe a case of an anti-ATP1A3-associated neurologic disorder. Mutations in the gene encoding this neuronal surface protein have already been recognized as the cause of infantile alternating hemiplegia, rapid-onset dystonia parkinsonism, and CAPOS syndrome. Although the autoantibodies are unlikely to be pathogenic, they are likely to be rare biomarkers for the apparently paraneoplastic neurologic syndrome or for the tumor itself.",
keywords = "Adenocarcinoma, Aged, Ataxia, Autoantibodies, Colonic Neoplasms, Female, HEK293 Cells, Humans, Immunoglobulin G, Neurons, Paraneoplastic Syndromes, Nervous System, Sodium-Potassium-Exchanging ATPase, Case Reports, Journal Article, Research Support, Non-U.S. Gov't",
author = "Madeleine Scharf and Ramona Miske and Fedor Heidenreich and Ralf Giess and Peter Landwehr and Inga-Madeleine Bl{\"o}cker and Nora Begemann and Yvonne Denno and Stephan Tiede and Cornelia D{\"a}hnrich and Wolfgang Schlumberger and Mandy Unger and Bianca Teegen and Winfried St{\"o}cker and Christian Probst and Lars Komorowski",
note = "{\textcopyright} 2015 American Academy of Neurology.",
year = "2015",
month = apr,
day = "21",
doi = "10.1212/WNL.0000000000001493",
language = "English",
volume = "84",
pages = "1673--9",
journal = "NEUROLOGY",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "16",

}

RIS

TY - JOUR

T1 - Neuronal Na+/K+ ATPase is an autoantibody target in paraneoplastic neurologic syndrome

AU - Scharf, Madeleine

AU - Miske, Ramona

AU - Heidenreich, Fedor

AU - Giess, Ralf

AU - Landwehr, Peter

AU - Blöcker, Inga-Madeleine

AU - Begemann, Nora

AU - Denno, Yvonne

AU - Tiede, Stephan

AU - Dähnrich, Cornelia

AU - Schlumberger, Wolfgang

AU - Unger, Mandy

AU - Teegen, Bianca

AU - Stöcker, Winfried

AU - Probst, Christian

AU - Komorowski, Lars

N1 - © 2015 American Academy of Neurology.

PY - 2015/4/21

Y1 - 2015/4/21

N2 - OBJECTIVES: To identify an autoreactivity in a 66-year-old woman who presented with combined brainstem and cerebellar syndrome including vertical gaze palsy, severe progressive ataxia, and spastic tetraparesis, an acute deterioration of vision, dysarthria, and dysphagia with concurrent diagnosis of a colon adenocarcinoma.METHODS: Patient's serum and CSF underwent comprehensive autoantibody screening by indirect immunofluorescence assay and immunoblot. For autoantigen purification, a histo-immunoprecipitation technique was developed followed by mass spectrometrical analysis. Recombinant candidate antigens were expressed in HEK293 and used to verify the identification.RESULTS: Indirect immunofluorescence assay screening revealed strong immunoglobulin G reactivity with neural tissues in serum and CSF, but not with a panel of 28 recombinantly expressed established neural autoantigens. The hitherto unknown target antigen was identified as the neuronal Na(+)/K(+) ATPase. Epitope mapping and competitive inhibition experiments showed that the autoantibodies were directed against the membrane-spanning alpha 3 subunit (ATP1A3) of the enzyme but did not bind to extracellular epitopes. Immunohistochemical analysis revealed overexpression of this subunit in the patient's tumor.CONCLUSIONS: We describe a case of an anti-ATP1A3-associated neurologic disorder. Mutations in the gene encoding this neuronal surface protein have already been recognized as the cause of infantile alternating hemiplegia, rapid-onset dystonia parkinsonism, and CAPOS syndrome. Although the autoantibodies are unlikely to be pathogenic, they are likely to be rare biomarkers for the apparently paraneoplastic neurologic syndrome or for the tumor itself.

AB - OBJECTIVES: To identify an autoreactivity in a 66-year-old woman who presented with combined brainstem and cerebellar syndrome including vertical gaze palsy, severe progressive ataxia, and spastic tetraparesis, an acute deterioration of vision, dysarthria, and dysphagia with concurrent diagnosis of a colon adenocarcinoma.METHODS: Patient's serum and CSF underwent comprehensive autoantibody screening by indirect immunofluorescence assay and immunoblot. For autoantigen purification, a histo-immunoprecipitation technique was developed followed by mass spectrometrical analysis. Recombinant candidate antigens were expressed in HEK293 and used to verify the identification.RESULTS: Indirect immunofluorescence assay screening revealed strong immunoglobulin G reactivity with neural tissues in serum and CSF, but not with a panel of 28 recombinantly expressed established neural autoantigens. The hitherto unknown target antigen was identified as the neuronal Na(+)/K(+) ATPase. Epitope mapping and competitive inhibition experiments showed that the autoantibodies were directed against the membrane-spanning alpha 3 subunit (ATP1A3) of the enzyme but did not bind to extracellular epitopes. Immunohistochemical analysis revealed overexpression of this subunit in the patient's tumor.CONCLUSIONS: We describe a case of an anti-ATP1A3-associated neurologic disorder. Mutations in the gene encoding this neuronal surface protein have already been recognized as the cause of infantile alternating hemiplegia, rapid-onset dystonia parkinsonism, and CAPOS syndrome. Although the autoantibodies are unlikely to be pathogenic, they are likely to be rare biomarkers for the apparently paraneoplastic neurologic syndrome or for the tumor itself.

KW - Adenocarcinoma

KW - Aged

KW - Ataxia

KW - Autoantibodies

KW - Colonic Neoplasms

KW - Female

KW - HEK293 Cells

KW - Humans

KW - Immunoglobulin G

KW - Neurons

KW - Paraneoplastic Syndromes, Nervous System

KW - Sodium-Potassium-Exchanging ATPase

KW - Case Reports

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1212/WNL.0000000000001493

DO - 10.1212/WNL.0000000000001493

M3 - SCORING: Journal article

C2 - 25809299

VL - 84

SP - 1673

EP - 1679

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 16

ER -