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...
Main Authors: | , , , , , , , , , , , , |
---|---|
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 |
id |
doaj-d6fe794e0c7648f7bb8dab6be13af2c5 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT youngeunpark plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT rushipenumarthy plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT paulpsun plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT carolineykang plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT mariechristinemorelkopp plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT jonathandowning plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT tarynngreen plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT traceyimmanuel plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT christophermward plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT deborahyoung plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT matthewjduring plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT palanbarber plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism AT maggielkalevzylinska plateletreactiveantibodiesinpatientsafterischaemicstrokeanepiphenomenonoranaturalprotectivemechanism |
_version_ |
1724447755315707904 |