Paraneoplastic Cerebellar Degeneration With P/Q-VGCC vs Yo Autoantibodies.

Antibodies, Neoplasm Autoantibodies CD8-Positive T-Lymphocytes Calcium Channels, Q-Type Humans Immunoglobulin G Nerve Tissue Proteins Paraneoplastic Cerebellar Degeneration

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
07 2022
Historique:
received: 31 01 2022
accepted: 14 04 2022
entrez: 7 9 2022
pubmed: 8 9 2022
medline: 11 9 2022
Statut: epublish

Résumé

Paraneoplastic cerebellar degeneration (PCD) is characterized by a widespread loss of Purkinje cells (PCs) and may be associated with autoantibodies against intracellular antigens such as Yo or cell surface neuronal antigens such as the P/Q-type voltage-gated calcium channel (P/Q-VGCC). Although the intracellular location of the target antigen in anti-Yo-PCD supports a T cell-mediated pathology, the immune mechanisms in anti-P/Q-VGCC-PCD remain unclear. In this study, we compare neuropathologic characteristics of PCD with anti-P/Q-VGCC and anti-Yo autoantibodies in an archival autopsy cohort. We performed neuropathology, immunohistochemistry, and multiplex immunofluorescence on formalin-fixed and paraffin-embedded brain tissue of 1 anti-P/Q-VGCC, 2 anti-Yo-PCD autopsy cases and controls. Anti-Yo-PCD revealed a diffuse and widespread PC loss together with microglial nodules with pSTAT1 Anti-Yo-PCD showed characteristic features of a T cell-mediated pathology, whereas this was not observed in 1 case of anti-P/Q-VGCC-PCD. Our findings support a pathogenic role of anti-P/Q-VGCC autoantibodies in causing neuronal dysfunction, probably due to altered synaptic transmission resulting in calcium dysregulation and subsequent PC death. Because disease progression may lead to irreversible PC loss, anti-P/Q-VGCC-PCD patients could benefit from early oncologic and immunologic therapies.

Sections du résumé

BACKGROUND AND OBJECTIVES
Paraneoplastic cerebellar degeneration (PCD) is characterized by a widespread loss of Purkinje cells (PCs) and may be associated with autoantibodies against intracellular antigens such as Yo or cell surface neuronal antigens such as the P/Q-type voltage-gated calcium channel (P/Q-VGCC). Although the intracellular location of the target antigen in anti-Yo-PCD supports a T cell-mediated pathology, the immune mechanisms in anti-P/Q-VGCC-PCD remain unclear. In this study, we compare neuropathologic characteristics of PCD with anti-P/Q-VGCC and anti-Yo autoantibodies in an archival autopsy cohort.
METHODS
We performed neuropathology, immunohistochemistry, and multiplex immunofluorescence on formalin-fixed and paraffin-embedded brain tissue of 1 anti-P/Q-VGCC, 2 anti-Yo-PCD autopsy cases and controls.
RESULTS
Anti-Yo-PCD revealed a diffuse and widespread PC loss together with microglial nodules with pSTAT1
DISCUSSION
Anti-Yo-PCD showed characteristic features of a T cell-mediated pathology, whereas this was not observed in 1 case of anti-P/Q-VGCC-PCD. Our findings support a pathogenic role of anti-P/Q-VGCC autoantibodies in causing neuronal dysfunction, probably due to altered synaptic transmission resulting in calcium dysregulation and subsequent PC death. Because disease progression may lead to irreversible PC loss, anti-P/Q-VGCC-PCD patients could benefit from early oncologic and immunologic therapies.

Identifiants

DOI: 10.1212/NXI.0000000000200006 PMID: 36070310 PMC: PMC9278121
pubmed: 36070310
pii: 9/4/e200006
doi: 10.1212/NXI.0000000000200006
pmc: PMC9278121
pii:
doi:

Substances chimiques

Antibodies, Neoplasm 0
Autoantibodies 0
Calcium Channels, Q-Type 0
Immunoglobulin G 0
Nerve Tissue Proteins 0
anti-Yo autoantibodies 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Austrian Science Fund FWF
ID : DOC 33
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : I 4685
Pays : Austria

Informations de copyright

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Michael Winklehner (M)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.
ORCID: 0000-0003-4938-7827

Jan Bauer (J)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Verena Endmayr (V)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Carmen Schwaiger (C)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Gerda Ricken (G)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.
ORCID: 0000-0003-0388-7965

Masakatsu Motomura (M)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Shunsuke Yoshimura (S)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Hiroshi Shintaku (H)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Kinya Ishikawa (K)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Yukio Tsuura (Y)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Takahiro Iizuka (T)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Takanori Yokota (T)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Takashi Irioka (T)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan.

Romana Höftberger (R)

From the Division of Neuropathology and Neurochemistry (M.W., V.E., C.S., G.R., R.H.), Department of Neurology, and Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; Department of Electrical and Electronics Engineering (M.M.), Faculty of Engineering, Nagasaki Institute of Applied Science; Department of Neurology and Strokology (S.Y.), Nagasaki University Hospital; Neurology Clinic with Neuromorphomics Laboratory (H.S.), Nitobe Memorial Nakano General Hospital, Tokyo; Division of Surgical Pathology (H.S.), Tokyo Medical and Dental University Hospital; The Center for Personalized Medicine for Healthy Aging (K.I.), Tokyo Medical and Dental University; Departments of Diagnostic Pathology and Clinical Laboratory (Y.T.), Yokosuka Kyosai Hospital, Kanagawa; Department of Neurology (T. Iizuka), Kitasato University School of Medicine, Kanagawa; Department of Neurology and Neurological Science (T.Y.), Graduate School, Tokyo Medical and Dental University; and Department of Neurology (T. Irioka), Yokosuka Kyosai Hospital, Kanagawa, Japan. romana.hoeftberger@meduniwien.ac.at.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antitumoraux › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Autoanticorps › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Canaux calciques › Canaux calciques de type N › Canaux calciques de type Q › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Paraneoplastic Cerebellar Degeneration With...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Syndromes neurologiques paranéoplasiques › Dégénérescence cérébelleuse paranéoplasique › Paraneoplastic Cerebellar Degeneration With...