Anti-NMDA-Receptor GluN1 Antibody Serostatus Is Robust in Acute Severe Stroke

Background: Anti-N-methyl-D-aspartate IgM and IgA antibodies (NMDAR1-abs) are associated with unfavorable stroke outcomes and may be risk factors thereof. However, to utilize NMDAR1-abs serostatus for risk assessment in acute stroke, it is crucial to understand the robustness of serostatus during this phase. Therefore, we investigated the robustness of NMDAR1-abs serostatus and titer levels up to seven days after stroke. Methods: In this exploratory analysis of the multicenter STRAWINSKI trial (identifier: NCT01264549), patients with severe ischemic stroke (NIHSS ≥ 9) in the middle cerebral artery territory were included. The first blood sample was taken within 36 h and then daily from day two to seven after stroke. NMDAR1-abs immunoglobulin (Ig)A and IgM were assessed in serum using cell-based assays. We initially measured NMDAR1-abs in the total cohort on day 1. Subsequently, in samples from seropositive and matched seronegative patients, we measured NMDAR1-abs on each following day. Titer dilutions started from 1:10 up to 1:1000. Seropositivity was defined as any titer > 0. Results: Out of 171 patients (mean age = 76 [SD = 11], median NIHSS = 15 [IQR = 12-18]), 16 (9%) individuals were seropositive. Seropositive patients remained seropositive and matched seronegative participants remained seronegative over sequential measurements. Although titer levels remained largely unchanged, some patients showed fluctuating titers. Conclusions: The status of NMDAR1-abs seropositivity is stable during acute stroke, with little to no variation in titer levels.