Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism

• Main Authors: Young Eun Park, Rushi Penumarthy, Paul P. Sun, Caroline Y. Kang, Marie-Christine Morel-Kopp, Jonathan Downing, Taryn N. Green, Tracey Immanuel, Christopher M. Ward, Deborah Young, Matthew J. During, P. Alan Barber, Maggie L. Kalev-Zylinska
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: thrombosis; stroke; autoantibodies; anti-platelet antibodies; platelet inhibition; neuroprotection
• Online Access: https://www.mdpi.com/1422-0067/21/21/8398
• ISSN: 1661-6596; 1422-0067

Ischaemic brain damage induces autoimmune responses, including the production of autoantibodies with potential neuroprotective effects. Platelets share unexplained similarities with neurons, and the formation of anti-platelet antibodies has been documented in neurological disorders. The aim of this study was to investigate the presence of anti-platelet antibodies in the peripheral blood of patients after ischaemic stroke and determine any clinical correlations. Using a flow cytometry-based platelet immunofluorescence method, we detected platelet-reactive antibodies in 15 of 48 (31%) stroke patients and two of 50 (4%) controls (<i>p</i> < 0.001). Western blotting revealed heterogeneous reactivities with platelet proteins, some of which overlapped with brain proteins. Stroke patients who carried anti-platelet antibodies presented with larger infarcts and more severe neurological dysfunction, which manifested as higher scores on the National Institutes of Health Stroke Scale (NIHSS; <i>p =</i> 0.009), but they had a greater recovery in the NIHSS by the time of hospital discharge (day 7 ± 2) compared with antibody-negative patients (<i>p</i> = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets (<i>p</i> = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% (<i>p <</i> 0.001), suggesting the potential to interfere with thrombus formation. In conclusion, platelet-reactive antibodies can be found in patients soon after ischaemic stroke and correlate with better short-term outcomes, suggesting a potential novel mechanism limiting thrombosis.