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

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...

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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:
Online Access:https://www.mdpi.com/1422-0067/21/21/8398
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spelling doaj-d6fe794e0c7648f7bb8dab6be13af2c52020-11-25T04:01:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218398839810.3390/ijms21218398Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective MechanismYoung Eun Park0Rushi Penumarthy1Paul P. Sun2Caroline Y. Kang3Marie-Christine Morel-Kopp4Jonathan Downing5Taryn N. Green6Tracey Immanuel7Christopher M. Ward8Deborah Young9Matthew J. During10P. Alan Barber11Maggie L. Kalev-Zylinska12Blood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandBlood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandBlood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandBlood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandDepartment of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney 2065, AustraliaNew Zealand Blood Service Centre, Auckland 1051, New ZealandBlood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandBlood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandDepartment of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney 2065, AustraliaDepartment of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland 1142, New ZealandCentre for Brain Research, University of Auckland, Auckland 1142, New ZealandCentre for Brain Research, University of Auckland, Auckland 1142, New ZealandBlood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New ZealandIschaemic 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.https://www.mdpi.com/1422-0067/21/21/8398thrombosisstrokeautoantibodiesanti-platelet antibodiesplatelet inhibitionneuroprotection
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism
International Journal of Molecular Sciences
thrombosis
stroke
autoantibodies
anti-platelet antibodies
platelet inhibition
neuroprotection
author_facet 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
author_sort Young Eun Park
title Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism
title_short Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism
title_full Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism
title_fullStr Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism
title_full_unstemmed Platelet-Reactive Antibodies in Patients after Ischaemic Stroke—An Epiphenomenon or a Natural Protective Mechanism
title_sort platelet-reactive antibodies in patients after ischaemic stroke—an epiphenomenon or a natural protective mechanism
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-11-01
description 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.
topic thrombosis
stroke
autoantibodies
anti-platelet antibodies
platelet inhibition
neuroprotection
url https://www.mdpi.com/1422-0067/21/21/8398
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