Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
J Neuroinflammation. 2024 Nov 4;21(1):286. doi: 10.1186/s12974-024-03269-3.
Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment.
Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing-remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches.
We identified alterations in peripheral and intrathecal adaptive immunity, mainly affecting the T cell (Tc) but also the B cell (Bc) compartment in ALE, RRMS, and pCNS-tumors compared to controls. ALE, RRMS, and pCNS-tumors featured higher expression of the T cell activation marker HLA-DR, which was even more pronounced in pCNS-tumors than in ALE or RRMS. Glioblastoma patients showed signs of T cell exhaustion that were not visible in RRMS patients. In-depth characterization of the PB revealed differences mainly in the T effector and memory compartment between RRMS and glioblastoma patients and similar alterations in the Bc compartment, including atypical Bc, CD19CD20 double negative Bc, and plasma cells. PB and CSF mFC together with CSF routine parameters could reliably differentiate ALE and RRMS from pCNS-tumors facilitating early diagnosis and treatment.
ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment.
免疫失调是中枢神经系统（CNS）自身免疫性疾病的标志，其特征为过度的免疫反应，而原发性中枢神经系统肿瘤（pCNS-肿瘤）表现出高度免疫抑制的实质微环境。
为了深入了解 CNS 自身免疫和脑肿瘤免疫的发病机制，我们通过流式细胞术（FC）分析了 81 例自身免疫性边缘脑炎（ALE）、148 例复发性缓解型多发性硬化症（RRMS）、33 例 IDH 野生型胶质瘤、9 例原发性中枢神经系统弥漫性大 B 细胞淋巴瘤（CNS-DLBCL）和 110 例对照者的外周血（PB）和脑脊液（CSF）。此外，通过 FC 结合无监督计算方法，对 20 例 RRMS 和 18 例 IDH 野生型胶质母细胞瘤患者与 19 例对照者的 PB 进行了深入的免疫表型分析。
我们发现外周和鞘内适应性免疫发生改变，主要影响 T 细胞（Tc），但与对照组相比，ALE、RRMS 和 pCNS-肿瘤中 B 细胞（Bc）也发生改变。与对照组相比，ALE、RRMS 和 pCNS-肿瘤中 T 细胞激活标志物 HLA-DR 的表达更高，在 pCNS-肿瘤中甚至比 ALE 或 RRMS 更为明显。胶质母细胞瘤患者表现出 T 细胞耗竭的迹象，而 RRMS 患者则没有这种迹象。PB 的深入特征分析主要显示 RRMS 和胶质母细胞瘤患者之间的 T 效应和记忆细胞群之间存在差异，以及 Bc 细胞群的相似改变，包括非典型 Bc、CD19CD20 双阴性 Bc 和浆细胞。PB 和 CSF mFC 与 CSF 常规参数一起可以可靠地区分 ALE 和 RRMS 与 pCNS-肿瘤，从而促进早期诊断和治疗。
ALE、RRMS 和 pCNS-肿瘤主要在 HLA-DR Tc、记忆 Tc、耗竭 Tc 和 Bc 亚群中表现出不同但部分重叠的变化，为发病机制提供了深入的了解。此外，mFC 具有诊断潜力，有助于早期诊断和治疗。
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