Blood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, New Zealand.
Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney 2065, Australia.
Int J Mol Sci. 2020 Nov 9;21(21):8398. doi: 10.3390/ijms21218398.
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 ( < 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; 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 ( = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets ( = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% ( 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.
脑缺血损伤可诱导自身免疫反应，包括产生具有潜在神经保护作用的自身抗体。血小板与神经元具有未明的相似性，在神经疾病中已发现抗血小板抗体的形成。本研究旨在调查缺血性中风后患者外周血中是否存在抗血小板抗体，并确定其与临床的相关性。通过基于流式细胞术的血小板免疫荧光法，我们在 48 例中风患者中的 15 例（31%）和 50 例对照者中的 2 例（4%）（<0.001）中检测到血小板反应性抗体。Western blot 显示与血小板蛋白的异质反应性，其中一些与脑蛋白重叠。携带抗血小板抗体的中风患者的梗死灶更大，神经功能障碍更严重，这表现为 NIHSS 评分更高（NIHSS；<0.009），但与抗体阴性患者相比，他们在出院时 NIHSS 的恢复更好（NIHSS；=0.043）。来自中风血清的抗体与激活的血小板反应更强烈（=0.031），并抑制血小板聚集高达 30.1±2.8%（<0.001），表明有可能干扰血栓形成。总之，缺血性中风后不久患者体内可检测到血小板反应性抗体，与更好的短期预后相关，提示一种潜在的限制血栓形成的新机制。
