title: Absence of antibodies to non-NMDA glutamate-receptor subunits in paraneoplastic cerebellar degeneration.
abstract: OBJECTIVE
  To determine whether patients with antineuronal antibody-associated paraneoplastic cerebellar degeneration (PCD) harbor antibodies to non-N-methyl-D-aspartate glutamate receptors (GluRs) in their serum.
  
  
  BACKGROUND
  A recent study identified antibodies to GluRs in the serum of patients with PCD.
  
  
  METHODS
  Sera of 35 patients with PCD (20 anti-Yo, 5 anti-Ri, 5 anti-Tr, and 5 anti-Hu) were examined by immunohistochemistry and immunoblot techniques. The expression of GluRs was obtained after transfection of 293T cells with cDNA plasmids corresponding to GluR1, GluR2, GluR3, GluR4, GluR6, and GluR7. The tumors of four patients with anti-Yo-associated PCD and nine ovarian carcinomas from patients without PCD were examined for the expression of GluRs.
  
  
  RESULTS
  The expression of each GluR subunit was confirmed using affinity-purified antibodies against the corresponding GluRs and with whole sera from two rabbits immunized with GluR3. Thirty-two sera from patients with PCD were negative and 3 showed equivocal reactivity with 293T cells expressing different GluRs. None of the 35 sera had a pattern of reactivity characteristic of any GluR antibody on immunohistochemistry of sections of rat brain. Eleven of 14 tumors did not express GluRs; only some cells of one paraneoplastic tumor expressed GluRs.
  
  
  CONCLUSIONS
  That patients with antibody-associated PCD (anti-Yo, -Ri, -Tr, and -Hu) harbor GluR antibodies in their sera is unlikely. GluR antibodies cannot be used as markers of paraneoplastic neurologic disorders.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Degenhardt
authors.forename: R M
authors.initials: RM
authors.lastname: Duvoisin
authors.forename: J
authors.initials: J
authors.lastname: Frennier
authors.forename: S H
authors.initials: SH
authors.lastname: Gultekin
authors.forename: M R
authors.initials: MR
authors.lastname: Rosenfeld
authors.forename: J B
authors.initials: JB
authors.lastname: Posner
authors.forename: J
authors.initials: J
authors.lastname: Dalmau
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D002526:Cerebellar Diseases / Q000276:immunology / Q000473:pathology*; D005260:Female; D015151:Immunoblotting; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000473:pathology; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D017470:Receptors, Glutamate