BACKGROUND AND PURPOSE: Antibodies against neuronal antigens develop in patients after stroke and some may serve as biomarkers of neuronal injury. We aimed to determine whether antibodies against subunit 1 (GluN1) of the N-methyl-D-aspartate receptor also develop after stroke and if so, whether they correlate with stroke characteristics. METHODS: Forty-eight patients with ischemic stroke and 96 healthy controls were tested for the presence of serum antibodies targeting GluN1. Testing was conducted using 20-kDa recombinant GluN1-S2 peptide (by ELISA and Western blotting) and on rat brain tissue (by Western blotting and immunohistochemistry). Clinical examinations and computed tomographic brain scans were performed to assess clinical state and infarct size and location. RESULTS: Of the 48 patients with ischemic stroke, 21 (44%) had antibodies that reacted with the recombinant GluN1-S2. There was no evidence of antibody binding to intact GluN1 in brain tissue. Western blot appearances suggested reactivity with GluN1 degradation products. Patients with anti-GluN1-S2 antibodies were more likely to have higher National Institutes of Health Stroke Scale scores, larger infarcts, and more frequent cortical involvement. Of the 96 controls, only 3 (3%), all aged>50 years, had antibodies that reacted with GluN1-S2 at low levels. CONCLUSIONS: Antibodies that bind recombinant GluN1-S2 peptides (but not the intact GluN1 protein) develop transiently in patients after stroke in proportion to infarct size, suggesting that these antibodies are raised secondarily to neuronal damage. The anti-GluN1-S2 antibodies may provide useful information about the presence and severity of cerebral infarction. This will require confirmation in larger studies.
BACKGROUND AND PURPOSE: Antibodies against neuronal antigens develop in patients after stroke and some may serve as biomarkers of neuronal injury. We aimed to determine whether antibodies against subunit 1 (GluN1) of the N-methyl-D-aspartate receptor also develop after stroke and if so, whether they correlate with stroke characteristics. METHODS: Forty-eight patients with ischemic stroke and 96 healthy controls were tested for the presence of serum antibodies targeting GluN1. Testing was conducted using 20-kDa recombinant GluN1-S2 peptide (by ELISA and Western blotting) and on rat brain tissue (by Western blotting and immunohistochemistry). Clinical examinations and computed tomographic brain scans were performed to assess clinical state and infarct size and location. RESULTS: Of the 48 patients with ischemic stroke, 21 (44%) had antibodies that reacted with the recombinant GluN1-S2. There was no evidence of antibody binding to intact GluN1 in brain tissue. Western blot appearances suggested reactivity with GluN1 degradation products. Patients with anti-GluN1-S2 antibodies were more likely to have higher National Institutes of Health Stroke Scale scores, larger infarcts, and more frequent cortical involvement. Of the 96 controls, only 3 (3%), all aged>50 years, had antibodies that reacted with GluN1-S2 at low levels. CONCLUSIONS: Antibodies that bind recombinant GluN1-S2 peptides (but not the intact GluN1 protein) develop transiently in patients after stroke in proportion to infarct size, suggesting that these antibodies are raised secondarily to neuronal damage. The anti-GluN1-S2 antibodies may provide useful information about the presence and severity of cerebral infarction. This will require confirmation in larger studies.
Authors: Andre L Samson; Simon T Nevin; David Croucher; Be'eri Niego; Philip B Daniel; Thomas W Weiss; Eliza Moreno; Denis Monard; Daniel A Lawrence; Robert L Medcalf Journal: J Neurochem Date: 2008-09-15 Impact factor: 5.372
Authors: Josep Dalmau; Erdem Tüzün; Hai-yan Wu; Jaime Masjuan; Jeffrey E Rossi; Alfredo Voloschin; Joachim M Baehring; Haruo Shimazaki; Reiji Koide; Dale King; Warren Mason; Lauren H Sansing; Marc A Dichter; Myrna R Rosenfeld; David R Lynch Journal: Ann Neurol Date: 2007-01 Impact factor: 10.422
Authors: Josep Dalmau; Amy J Gleichman; Ethan G Hughes; Jeffrey E Rossi; Xiaoyu Peng; Meizan Lai; Scott K Dessain; Myrna R Rosenfeld; Rita Balice-Gordon; David R Lynch Journal: Lancet Neurol Date: 2008-10-11 Impact factor: 44.182
Authors: Changiz Taghibiglou; Henry G S Martin; Ted Weita Lai; Taesup Cho; Shiv Prasad; Luba Kojic; Jie Lu; Yitao Liu; Edmund Lo; Shu Zhang; Julia Z Z Wu; Yu Ping Li; Yan Hua Wen; Joon-Hyuk Imm; Max S Cynader; Yu Tian Wang Journal: Nat Med Date: 2009-11-22 Impact factor: 53.440
Authors: Hongjie Yuan; Katie M Vance; Candice E Junge; Matthew T Geballe; James P Snyder; John R Hepler; Manuel Yepes; Chian-Ming Low; Stephen F Traynelis Journal: J Biol Chem Date: 2009-02-24 Impact factor: 5.157
Authors: Georg Royl; Tsafack Judicael Fokou; Rittika Chunder; Rakad Isa; Thomas F Münte; Klaus-Peter Wandinger; Markus Schwaninger; Oliver Herrmann; José Manuel Valdueza; Jan Brocke; Martin Willkomm; Dietrich Willemsen; Gerd U Auffarth; Swantje Mindorf; Britta Brix; Angel Chamorro; Anna Planas; Xabier Urra Journal: J Neurol Date: 2019-07-29 Impact factor: 4.849
Authors: Edward Gomperts; John D Belcher; Leo E Otterbein; Thomas D Coates; John Wood; Brett E Skolnick; Howard Levy; Gregory M Vercellotti Journal: Am J Hematol Date: 2017-04-29 Impact factor: 10.047
Authors: Jonathan Howard DeLong; Sarah Naomi Ohashi; Kevin Charles O'Connor; Lauren Hachmann Sansing Journal: Semin Immunopathol Date: 2022-06-29 Impact factor: 11.759
Authors: Mitchell S V Elkind; Amelia K Boehme; Craig J Smith; Andreas Meisel; Marion S Buckwalter Journal: Stroke Date: 2020-09-08 Impact factor: 7.914