LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor

Elena Koustova, Yoshitatsu Sei, Linda Fossom, Mei Ling Wei, Peter N R Usherwood, N. Bradley Keele, Michael A Rogawski, Anthony S. Basile

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Autoantibodies to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors may contribute to chronic hyperexcitability syndromes and neurodegeneration, but their origin is unclear. We examined LP-BM5 murine leukemia virus-infected mice, which manifest excitotoxic brain lesions and hypergammaglobulinemia, for the presence of AMPA-receptor Ab's. Endogenous IgG accumulated upon neurons in the neocortex and caudate/putamen of infected mice and interacted with native and recombinant AMPA-receptor subunits with the following relative abundance: GluR3 ≥ GluR1 > GluR2 = GluR4, as determined by immunoprecipitation. In a radioligand assay, IgG preparations from infected mice specifically inhibited [3H]AMPA binding to receptors in brain homogenates, an activity that was lost after preadsorbing the IgG preparation to immobilized LP-BM5 virus. These IgGs also evoked currents when applied to hippocampal pyramidal neurons or to damaged cerebellar granule neurons. These currents could be blocked using any of several AMPA receptor antagonists. Thus, anti-AMPA-receptor Ab's can be produced as the result of a virus infection, in part through molecular mimicry. These Ab's may alter neuronal signaling and contribute to the neurodegeneration observed in these mice, actions that may be curtailed by the use of AMPA-receptor antagonists.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalJournal of Clinical Investigation
Volume107
Issue number6
StatePublished - 2001
Externally publishedYes

Fingerprint

Autoantibodies
Viruses
Immunoglobulin G
Molecular Mimicry
Hypergammaglobulinemia
Neurons
Murine Leukemia Viruses
Radioligand Assay
Pyramidal Cells
Putamen
Neocortex
Brain
Virus Diseases
bucide
propionic acid
Immunoprecipitation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Koustova, E., Sei, Y., Fossom, L., Wei, M. L., Usherwood, P. N. R., Keele, N. B., ... Basile, A. S. (2001). LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor. Journal of Clinical Investigation, 107(6), 737-744.

LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor. / Koustova, Elena; Sei, Yoshitatsu; Fossom, Linda; Wei, Mei Ling; Usherwood, Peter N R; Keele, N. Bradley; Rogawski, Michael A; Basile, Anthony S.

In: Journal of Clinical Investigation, Vol. 107, No. 6, 2001, p. 737-744.

Research output: Contribution to journalArticle

Koustova, E, Sei, Y, Fossom, L, Wei, ML, Usherwood, PNR, Keele, NB, Rogawski, MA & Basile, AS 2001, 'LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor', Journal of Clinical Investigation, vol. 107, no. 6, pp. 737-744.
Koustova E, Sei Y, Fossom L, Wei ML, Usherwood PNR, Keele NB et al. LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor. Journal of Clinical Investigation. 2001;107(6):737-744.
Koustova, Elena ; Sei, Yoshitatsu ; Fossom, Linda ; Wei, Mei Ling ; Usherwood, Peter N R ; Keele, N. Bradley ; Rogawski, Michael A ; Basile, Anthony S. / LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 6. pp. 737-744.
@article{674e73efc40746a19b5c5025816fd2ce,
title = "LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor",
abstract = "Autoantibodies to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors may contribute to chronic hyperexcitability syndromes and neurodegeneration, but their origin is unclear. We examined LP-BM5 murine leukemia virus-infected mice, which manifest excitotoxic brain lesions and hypergammaglobulinemia, for the presence of AMPA-receptor Ab's. Endogenous IgG accumulated upon neurons in the neocortex and caudate/putamen of infected mice and interacted with native and recombinant AMPA-receptor subunits with the following relative abundance: GluR3 ≥ GluR1 > GluR2 = GluR4, as determined by immunoprecipitation. In a radioligand assay, IgG preparations from infected mice specifically inhibited [3H]AMPA binding to receptors in brain homogenates, an activity that was lost after preadsorbing the IgG preparation to immobilized LP-BM5 virus. These IgGs also evoked currents when applied to hippocampal pyramidal neurons or to damaged cerebellar granule neurons. These currents could be blocked using any of several AMPA receptor antagonists. Thus, anti-AMPA-receptor Ab's can be produced as the result of a virus infection, in part through molecular mimicry. These Ab's may alter neuronal signaling and contribute to the neurodegeneration observed in these mice, actions that may be curtailed by the use of AMPA-receptor antagonists.",
author = "Elena Koustova and Yoshitatsu Sei and Linda Fossom and Wei, {Mei Ling} and Usherwood, {Peter N R} and Keele, {N. Bradley} and Rogawski, {Michael A} and Basile, {Anthony S.}",
year = "2001",
language = "English (US)",
volume = "107",
pages = "737--744",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - LP-BM5 virus-infected mice produce activating autoantibodies to the AMPA receptor

AU - Koustova, Elena

AU - Sei, Yoshitatsu

AU - Fossom, Linda

AU - Wei, Mei Ling

AU - Usherwood, Peter N R

AU - Keele, N. Bradley

AU - Rogawski, Michael A

AU - Basile, Anthony S.

PY - 2001

Y1 - 2001

N2 - Autoantibodies to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors may contribute to chronic hyperexcitability syndromes and neurodegeneration, but their origin is unclear. We examined LP-BM5 murine leukemia virus-infected mice, which manifest excitotoxic brain lesions and hypergammaglobulinemia, for the presence of AMPA-receptor Ab's. Endogenous IgG accumulated upon neurons in the neocortex and caudate/putamen of infected mice and interacted with native and recombinant AMPA-receptor subunits with the following relative abundance: GluR3 ≥ GluR1 > GluR2 = GluR4, as determined by immunoprecipitation. In a radioligand assay, IgG preparations from infected mice specifically inhibited [3H]AMPA binding to receptors in brain homogenates, an activity that was lost after preadsorbing the IgG preparation to immobilized LP-BM5 virus. These IgGs also evoked currents when applied to hippocampal pyramidal neurons or to damaged cerebellar granule neurons. These currents could be blocked using any of several AMPA receptor antagonists. Thus, anti-AMPA-receptor Ab's can be produced as the result of a virus infection, in part through molecular mimicry. These Ab's may alter neuronal signaling and contribute to the neurodegeneration observed in these mice, actions that may be curtailed by the use of AMPA-receptor antagonists.

AB - Autoantibodies to α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors may contribute to chronic hyperexcitability syndromes and neurodegeneration, but their origin is unclear. We examined LP-BM5 murine leukemia virus-infected mice, which manifest excitotoxic brain lesions and hypergammaglobulinemia, for the presence of AMPA-receptor Ab's. Endogenous IgG accumulated upon neurons in the neocortex and caudate/putamen of infected mice and interacted with native and recombinant AMPA-receptor subunits with the following relative abundance: GluR3 ≥ GluR1 > GluR2 = GluR4, as determined by immunoprecipitation. In a radioligand assay, IgG preparations from infected mice specifically inhibited [3H]AMPA binding to receptors in brain homogenates, an activity that was lost after preadsorbing the IgG preparation to immobilized LP-BM5 virus. These IgGs also evoked currents when applied to hippocampal pyramidal neurons or to damaged cerebellar granule neurons. These currents could be blocked using any of several AMPA receptor antagonists. Thus, anti-AMPA-receptor Ab's can be produced as the result of a virus infection, in part through molecular mimicry. These Ab's may alter neuronal signaling and contribute to the neurodegeneration observed in these mice, actions that may be curtailed by the use of AMPA-receptor antagonists.

UR - http://www.scopus.com/inward/record.url?scp=0035103936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035103936&partnerID=8YFLogxK

M3 - Article

C2 - 11254673

AN - SCOPUS:0035103936

VL - 107

SP - 737

EP - 744

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -