Department of Epileptology, University of Bonn Medical Center, Venusberg - Campus 1, 53127 Bonn, Germany; Department of Psychiatry and Psychotherapy, University Medicine Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany.
Department of Epileptology, University of Bonn Medical Center, Venusberg - Campus 1, 53127 Bonn, Germany.
Epilepsy Behav. 2020 May;106:107016. doi: 10.1016/j.yebeh.2020.107016. Epub 2020 Mar 18.
Flow cytometry helps to elucidate the cellular immune repertoire's mechanisms in patients with temporal lobe epilepsy (TLE) due to limbic encephalitis (LE) subcategories and carries potential significance for subtype-specific treatment.
We enrolled 62 patients with TLE due to LE associated with no autoantibodies (n = 40), neural autoantibodies (n = 22), as well as autoantibodies against intracellular antigens (n = 15/22). All patients underwent neuropsychological testing, brain magnetic resonance imaging (MRI), electroencephalography (EEG) recordings, and peripheral blood (PB) and cerebrospinal fluid (CSF) investigations including flow cytometry.
CD19+ B-cells were increased in the PB and CSF of patients with antibody-negative LE compared with those associated with antibodies against intracellular antigens (Kruskal-Wallis one way analysis of variance (ANOVA) on ranks with Dunn's test, p < 0.05). There were no differences in CD138+ B-cells, CD4+ T-cells, human leukocyte antigen - DR isotype (HLA-DR+) CD4+ T-cells, CD8+ T-cells, and HLA-DR+ CD8+ T-cells in the CSF between groups with LE. The blood-brain barrier is more often impaired in patients with antibody-negative LE than in LE with antibodies against intracellular antigens (chi-square test, p < 0.05). In addition, we detected no correlations between immune cell subsets and clinical or paraclinical parameters in patients with antibody-negative and intracellular antibody-positive LE.
The increase of CD19+ B-cells in the CSF and frequent signs of dysfunctional blood-brain barrier in patients with antibody-negative rather than intracellular antibody-positive LE suggest that CD19+ B-cells play a role in antibody-negative encephalitis although their pathogenic role in the central nervous system (CNS) immunity because of missing correlations between immune cells and clinical and paraclinical parameters remains unknown. Further studies are required to evaluate the usefulness of these B-cells as a biomarker for the stratification of treatment strategies.
流式细胞术有助于阐明由于边缘脑炎（LE）亚类导致的颞叶癫痫（TLE）患者的细胞免疫受体机制，并对针对特定亚型的治疗具有潜在意义。
我们纳入了 62 名由 LE 引起的 TLE 患者，这些患者不伴有自身抗体（n=40）、神经自身抗体（n=22）和针对细胞内抗原的自身抗体（n=22/15）。所有患者均接受神经心理学测试、脑磁共振成像（MRI）、脑电图（EEG）记录以及外周血（PB）和脑脊液（CSF）检查，包括流式细胞术。
与针对细胞内抗原的抗体阴性 LE 患者相比，抗体阴性 LE 患者的 PB 和 CSF 中 CD19+B 细胞增加（Kruskal-Wallis 单向方差分析（ANOVA）秩和检验，Dunn 检验，p<0.05）。LE 患者中 CSF 中 CD138+B 细胞、CD4+T 细胞、人类白细胞抗原 - DR 同种型（HLA-DR+）CD4+T 细胞、CD8+T 细胞和 HLA-DR+CD8+T 细胞之间无差异。与针对细胞内抗原的抗体阳性 LE 患者相比，抗体阴性 LE 患者的血脑屏障更常受损（卡方检验，p<0.05）。此外，我们在抗体阴性和细胞内抗体阳性 LE 患者中均未发现免疫细胞亚群与临床或临床前参数之间存在相关性。
与针对细胞内抗原的抗体阳性 LE 患者相比，抗体阴性而非细胞内抗体阳性 LE 患者的 CSF 中 CD19+B 细胞增加以及血脑屏障功能障碍的常见迹象表明，尽管由于免疫细胞与临床和临床前参数之间缺乏相关性，CD19+B 细胞在中枢神经系统（CNS）免疫中的致病作用仍未知，但 CD19+B 细胞在抗体阴性脑炎中发挥作用。需要进一步研究来评估这些 B 细胞作为治疗策略分层的生物标志物的有用性。
