High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms.
High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms.
复制标题
有神经系统症状的COVID-19患者脑脊液自身抗体的高频率。
DOI：
10.1016/j.bbi.2020.12.022
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Prüß H
中科院分区：
文献类型：
--
作者：
Franke C;Ferse C;Kreye J;Reincke SM;Sanchez-Sendin E;Rocco A;Steinbrenner M;Angermair S;Treskatsch S;Zickler D;Eckardt KU;Dersch R;Hosp J;Audebert HJ;Endres M;Ploner JC;Prüß H
COVID-19重症监护患者可能会出现神经系统综合征，通常是在脑脊液（CSF）中没有SARS-CoV-2的情况下。最近发现一些病毒中和抗体与脑组织交叉反应，提示可能涉及特异性自身免疫。对11名出现不明原因神经系统症状（包括肌阵挛、眼功能障碍、谵妄、肌张力障碍和癫痫发作）的重症COVID-19患者的血液和CSF样本进行了抗神经元和抗神经胶质自身抗体分析。使用基于细胞的测定和间接免疫荧光法对未固定的小鼠脑切片，所有患者的血清或CSF中均显示抗神经元自身抗体。抗原包括细胞内和神经元表面蛋白，如Yo或NMDA受体，但也包括各种特异性未确定的表位，使人联想到用某些人单克隆SARS-CoV-2抗体观察到的脑组织结合。这些包括血管内皮，星形胶质细胞蛋白和基底节，海马或嗅球的神经胶质细胞。在没有其他解释的情况下，靶向大脑的自身抗体的频率很高，这表明与临床症状，特别是与过度兴奋（肌阵挛、癫痫发作）存在因果关系。一些潜在的自身抗原及其与SARS-CoV-2的潜在分子模拟仍有待鉴定。然而，自身抗体现在可能已经解释了COVID-19多器官疾病的某些方面，并可以指导选定病例的免疫治疗。
COVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 in cerebrospinal fluid (CSF). The recent finding of some virus-neutralizing antibodies cross-reacting with brain tissue suggests the possible involvement of specific autoimmunity. Blood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including myoclonus, oculomotor disturbance, delirium, dystonia and epileptic seizures, were analyzed for anti-neuronal and anti-glial autoantibodies. Using cell-based assays and indirect immunofluorescence on unfixed murine brain sections, all patients showed anti-neuronal autoantibodies in serum or CSF. Antigens included intracellular and neuronal surface proteins, such as Yo or NMDA receptor, but also various specific undetermined epitopes, reminiscent of the brain tissue binding observed with certain human monoclonal SARS-CoV-2 antibodies. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still await identification. However, autoantibodies may already now explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.
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DOI：
10.1016/s1474-4422(20)30308-2
发表时间：
2020-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Matschke J;Lütgehetmann M;Hagel C;Sperhake JP;Schröder AS;Edler C;Mushumba H;Fitzek A;Allweiss L;Dandri M;Dottermusch M;Heinemann A;Pfefferle S;Schwabenland M;Sumner Magruder D;Bonn S;Prinz M;Gerloff C;Püschel K;Krasemann S;Aepfelbacher M;Glatzel M
通讯作者：
Glatzel M
DOI：
10.1016/s1474-4422(18)30244-8
发表时间：
2018-09
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Armangue T;Spatola M;Vlagea A;Mattozzi S;Cárceles-Cordon M;Martinez-Heras E;Llufriu S;Muchart J;Erro ME;Abraira L;Moris G;Monros-Giménez L;Corral-Corral Í;Montejo C;Toledo M;Bataller L;Secondi G;Ariño H;Martínez-Hernández E;Juan M;Marcos MA;Alsina L;Saiz A;Rosenfeld MR;Graus F;Dalmau J;Spanish Herpes Simplex Encephalitis Study Group
通讯作者：
Spanish Herpes Simplex Encephalitis Study Group
影响因子：
5.3
作者：
Liotta EM;Batra A;Clark JR;Shlobin NA;Hoffman SC;Orban ZS;Koralnik IJ
通讯作者：
Koralnik IJ
影响因子：
29
作者：
Fang, Boyan;McKeon, Andrew;Lennon, Vanda A.
通讯作者：
Lennon, Vanda A.
影响因子：
64.5
作者：
Kreye J;Reincke SM;Kornau HC;Sánchez-Sendin E;Corman VM;Liu H;Yuan M;Wu NC;Zhu X;Lee CD;Trimpert J;Höltje M;Dietert K;Stöffler L;von Wardenburg N;van Hoof S;Homeyer MA;Hoffmann J;Abdelgawad A;Gruber AD;Bertzbach LD;Vladimirova D;Li LY;Barthel PC;Skriner K;Hocke AC;Hippenstiel S;Witzenrath M;Suttorp N;Kurth F;Franke C;Endres M;Schmitz D;Jeworowski LM;Richter A;Schmidt ML;Schwarz T;Müller MA;Drosten C;Wendisch D;Sander LE;Osterrieder N;Wilson IA;Prüss H
通讯作者：
Prüss H