Table 2.

Impact of anti-AMPA antibodies in the CNS: preclinical evidences.

Source	Targeted GluA Subunit	Experimental Paradigm	Effects	Reference
Serum of rabbits immunized with a specific amino acid sequence of the GluR3 protein (the Glu3B peptide, aa 372–395) Purified IgG anti-GluA3 autoantibodies Serum from patients with active Rasmussen’s	GluA3	Cultured fetal mouse cortical neurons	↑ Currents in neurons, prevented by CNQX The GluR3B peptide specifically blocks the antisera- and IgG-evoked currents The anti-GluR3B antibody mimics the serum from immunized rabbit and the purified IgG.	[73]
Murine antibody recognizing a specific sequence of the GluR3 protein (the Glu3B peptide, aa 372–395)	GluA3	Mouse coronal slices of somatosensory cortex Primary hippocampal cultures	Immunostaining of neurons ↑ CNQX-sensitive currents in neurons GluR3B peptide-induced neuronal death reduced by CNQX	[105]
Anti-GluA3 IgG isolated from GluA3 (aa 246–455)-immunized rabbits	GluA3	Rat mixed cortical neuronal and glial cultures Whole cell recording in cultured rat cortical neurons	↑ Release of LDH from mixed cultures in a GIKY52466 or CNQX-independent manner The plasma from immunized animals does not evoke currents in cultured neurons	[112]
Purified rabbit antibody recognizing a specific amino acid sequence of the GluR3 protein (the Glu3B peptide, aa 372–395) Monoclonal mouse anti-GluA3B	GluA3	Rat brain homogenates Xenopus laevi oocytes expressing GluA3 homomeric or GluA2/A3 heteromeric AMPARs	Purified rabbit anti-GluA3 antibody elicits whole cell currents that were sensitive to CNQX	[98]
Murine anti-autoantibody recognizing the amino acid sequence of the GluR3 protein (the Glu3B peptide, aa 372–395)	GluA3	DBA/2J mice immunized with the GluR3B peptide that express circulating anti-GluA3B autoantibodies	Immunized DBA/2J mice were more susceptible to pentetrazol-induced seizures	[106]
Serum and CSF containing anti-GluA3 autoantibodies from patients suffering from FTD	GluA3	Rat hippocampal neuronal primary cultures differentiated neurons from human-induced pluripotent stem cells (hIPSC)	↓ GluA3 subunit synaptic localization of AMPA receptor in hippocampal neuronal primary cultures ↓ Dendritic spines AMPA receptor in cultured hippocampal neurons ↓ GluA3 subunit fraction in the postsynaptic fraction of cultured hIPSC	[58]
Serum of patients suffering from FTD-Tau neuropathology with a high titer of anti-GluA3 autoantibody	GluA3	Mouse cortical synaptosomes	The serum does not evoke glutamate exocytosis ↓ AMPA-evoked glutamate release	[103]
Commercial anti-GluA3 antibody	GluA3	Mouse cortical synaptosomes	↑ GluA2 and GluA3 subunits insertion in synaptosomal plasma membranes The antibody does not evoke glutamate exocytosis ↑ AMPA-evoked glutamate release	[104]
IgG Anti-GluA3 antibody from rabbit immunized with the GluR3B peptide	GluA3	Mouse whole brain lysates Primary hippocampal neurons	Anti-GluA3 immunostaining in the whole brain lysate ↓ excitatory postsynaptic currents (EPSCs) in primary hippocampal neurons	[108]
Serum of a patient suffering from progressive sporadic olivopontocerebellar atrophy Purified IgM anti-GluA2 autoantibodies	GluA2	Cultured fetal mouse cortical neurons	↑ Currents in neurons in a CNQX-sensitive manner Currents were blocked by a synthetic peptide corresponding to the specific epitope region of GluR2 (aa 369–393)	[111]
Purified IgM anti-GluA1 and GluA2 autoantibodies from the CSF of patients suffering from anti-AMPA receptor encephalitis Commercial anti-GluA1 and GluA2 antibody	GluA2	Primary rat hippocampal neuron and astrocyte cocultures	↓ Surface AMPA receptor protein and synaptic localization Unmodified glutamatergic synapse density and cell viability ↑ Internalization of AMPA receptor clusters ↓ Miniature excitatory postsynaptic currents (mEPSCs) ↓ Miniature inhibitory postsynaptic currents (mIPSCs) ↑Intrinsic neuronal excitability after 48 h of treatment with patient CSF Commercial anti-GluA2 antibody does not cause receptor internalization	[102]
Anti-GluA2 autoantibodies purified from patients suffering from limbic encephalitis	GluA2	Human embryonic kidney 293 (HEK293) cells	↓ GluA2-containing AMPA receptor clusters number at synapses with a smaller decrease in overall AMPA receptor cluster density	[101]
Commercial anti-GluA2 antibody	GluA2	Mouse cortical synaptosomes	↑ Insertion of GluA2 and GluA3 subunits in synaptosomal plasma membranes The anti-GluA2 antibody does not evoke glutamate exocytosis ↑ AMPA-evoked glutamate release	[104]
Purified IgM anti-GluA1 autoantibodies from the CSF of anti-AMPA receptor encephalitis patients Commercial anti-GluA1 antibody	GluA1	Primary rat hippocampal neuron and astrocyte cocultures	↓ Localization of synaptic surface AMPA receptor protein The anti-GluA1 antibody does not modify the glutamatergic synapse density and the cell viability ↑ Internalization of AMPA receptor clusters ↓ Miniature excitatory postsynaptic currents (mEPSCs) ↓ Miniature inhibitory postsynaptic currents (mIPSCs) ↑ Intrinsic neuronal excitability after 48 h of treatment with patient CSF Commercial anti-GluA1 antibody does not cause receptor internalization	[102]
Commercial anti-GluA1 antibody	GluA1	Mouse cortical synaptosomes	The anti-GluA1 antibody does not evoke glutamate exocytosis The anti-GluA1 antibody does not modify the AMPA-evoked glutamate release	[104]