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Blood Test Detecting Autoantibodies to N-Methyl-D-aspartate Neuroreceptors for Evaluation of Patients with Transient Ischemic Attack and Stroke

¹ Department of Neurology and Neurosurgery, I.P. Pavlov’s State Medical University, 6/8 Tolstoj Str., St. Petersburg, Russia 197102.

² Clinic of Neurology, Institute of Human Brain, 9a Pavlov Street, St. Petersburg, Russia 197376.

^aAddress for correspondence to this author: Department of Chemistry, Emory University, Atwood Bldg., 1515 Pierce Dr., Atlanta, GA 30322. Fax 404-633-9494; e-mail sdambin{at}emory.edu.

Abstract

Background: Stroke is a multisystemic disorder that includes mechanisms of thrombosis and neurotoxic coupling. Key metabolites of the molecular cascade following biochemical events appear simultaneously in brain tissue, the blood–brain barrier, and brain vessels, activating the immune system and generating autoantibodies (aAbs) to brain-specific antigens. We developed an ELISA blood test to measure aAbs to a subtype of N-methyl-D-aspartate (NMDA) receptors, which are the key markers of neurotoxicity underlying cerebral ischemia. We investigated the diagnostic accuracy of serum aAbs to NR2A/2B, a subtype of NMDA receptors, in assessing transient ischemic attack (TIA) and ischemic stroke (IS) and its ability to distinguish cerebral ischemia from intracerebral hemorrhage (ICH).

Methods: Autoantibodies to NR2A/2B were measured in 360 serum samples: 105 from TIA/stroke patients and 255 from controls, including patients with controlled hypertension/atherosclerosis and gender- and age-matched healthy individuals.

Results: Patients with TIA (n = 56) and acute IS (n = 31) had significantly higher NR2A/2B aAb concentrations than controls (P <0.0001). The test sensitivities for TIA and IS were 95% and 97%, respectively, and predictive values were 86% and 91% at a cutoff point of 2.0 µg/L. The area under the ROC curve was 0.99. Monitoring NR2A/2B aAbs within 72 h differentiated IS and ICH (P <0.001) and was confirmed by magnetic resonance imaging and computed tomography.

Conclusions: NR2A/2B aAbs are independent and sensitive serologic markers capable of detecting TIA with a high posttest probability and, in conjunction with neurologic observation and neuroimaging, ruling out ICH. The test may help assess risk of TIA in routine general practice and may potentially be useful in assisting diagnosis of acute IS in the emergency setting.

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