Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Brain Behav Immun. 2023 Mar;109:139-143. doi: 10.1016/j.bbi.2023.01.006. Epub 2023 Jan 16.
Neurological symptoms, in particular cognitive deficits, are common in post-COVID-19 syndrome (PCS). There is no approved therapy available, and the underlying disease mechanisms are largely unknown. Besides others, autoimmune processes may play a key role.
We here present data of a prospective study conducted between September 2020 and December 2021 and performed at two German University hospitals with specialized Neurology outpatient clinics. Fifty patients with self-reported cognitive deficits as main complaint of PCS and available serum and CSF samples were included. Cell-based assays and indirect immunofluorescence on murine brain sections were used to detect autoantibodies against intracellular and surface antigens in serum and CSF and analyzed for associations with cognitive screening assessment.
Clearly abnormal cognitive status (MoCA ≤ 25/30 points) was only seen in 18/50 patients with self-reported cognitive deficits. Most patients (46/50) had normal routine CSF parameters. anti-neuronal autoantibodies were found in 52 % of all patients: n = 9 in serum only, n = 3 in CSF only and n = 14 in both, including those against myelin, Yo, Ma2/Ta, GAD65 and NMDA receptor, but also a variety of undetermined epitopes on brain sections. These included cerebral vessel endothelium, Purkinje neurons, granule cells, axon initial segments, astrocytic proteins and neuropil of basal ganglia or hippocampus as well as a formerly unknown perinuclear rim pattern. Pathological MoCA results were associated with the presence of anti-neuronal antibodies in CSF (p = 0.0004).
Autoantibodies targeting brain epitopes are common in PCS patients and strongly associate with pathological cognitive screening tests, in particular when found in CSF. Several underlying autoantigens still await experimental identification. Further research is needed to inform on the clinical relevance of these autoantibodies, including controlled studies that explore the potential efficacy of antibody-depleting immunotherapy in PCS.
新冠后综合征（PCS）患者常出现神经系统症状，特别是认知障碍。目前尚无获批的治疗方法，其潜在发病机制也知之甚少。除其他因素外，自身免疫过程可能发挥关键作用。
本研究为前瞻性研究，于 2020 年 9 月至 2021 年 12 月在两家德国大学附属医院的神经内科门诊进行。共纳入 50 例以认知障碍为主要表现且有血清和脑脊液样本的 PCS 患者。采用细胞检测和鼠脑切片间接免疫荧光法检测血清和脑脊液中针对细胞内和细胞表面抗原的自身抗体，并分析其与认知筛查评估的相关性。
仅有 18/50 例自述认知障碍的患者存在明显的认知障碍（MoCA≤25/30 分）。大多数患者（46/50）的常规脑脊液参数正常。所有患者中有 52%存在神经元自身抗体：9 例仅在血清中，3 例仅在脑脊液中，14 例在血清和脑脊液中均存在，包括针对髓鞘、Yo、Ma2/Ta、GAD65 和 NMDA 受体的抗体，以及针对脑切片中各种未确定表位的抗体，包括脑小血管内皮细胞、浦肯野神经元、颗粒细胞、轴突起始段、星形胶质细胞蛋白和基底节或海马神经毡，以及一种以前未知的核周边缘模式。病理性 MoCA 结果与 CSF 中存在神经元自身抗体相关（p=0.0004）。
针对脑表位的自身抗体在 PCS 患者中很常见，与病理性认知筛查检测结果强烈相关，尤其是在脑脊液中发现时。还有一些潜在的自身抗原仍有待实验鉴定。需要进一步研究以了解这些自身抗体的临床意义，包括探索抗体耗竭免疫疗法在 PCS 中的潜在疗效的对照研究。
