Harrer A, Pilz G, Wipfler P, Oppermann K, Sellner J, Hitzl W, Haschke-Becher E, Afazel S, Rispens T, van der Kleij D, Trinka E, Kraus J
Department of Neurology, Paracelsus Medical University, Salzburg, Austria.
Department of Neurology, Klinikum rechts der Isar, Technische Universät München, Germany.
Clin Exp Immunol. 2015 Jun;180(3):383-92. doi: 10.1111/cei.12590. Epub 2015 Apr 27.
Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell-bound NZB, adhesion molecule (AM) expression and the treatment-associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T cells from 10 patients with non-inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower NZB saturation levels (P<0.02) and a higher surface expression of ICAM-1 and LFA-1 (P<0.001) were observed on CSF CD8 T cells. CSF T cell ratios (0.3-2.1) and NZB concentrations (0.01-0.42 µg/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell-bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.
在接受那他珠单抗（NZB）治疗的多发性硬化症（MS）患者的脑脊液（CSF）中，白细胞计数显著降低，CD4/CD8 T细胞比率降低，这可能对中枢神经（CNS）免疫监视产生影响。关于与NZB相关的进行性多灶性白质脑病，我们旨在确定游离NZB、细胞结合NZB、黏附分子（AM）表达与CSF T细胞比率的治疗相关变化之间的关系。研究了15例接受NZB治疗的MS患者的外周血（PB）和CSF T细胞，以及10例非炎性神经系统疾病患者和5例新诊断MS患者的CSF T细胞。通过流式细胞术分析细胞间黏附分子-1（ICAM-1）、白细胞功能抗原-1（LFA-1）、极晚期活化抗原-4（VLA-4）、NZB饱和水平和T细胞比率。通过酶联免疫吸附测定（ELISA）测量NZB浓度。在CSF CD8 T细胞上观察到较低的NZB饱和水平（P<0.02）以及ICAM-1和LFA-1的较高表面表达（P<0.001）。CSF T细胞比率（0.3 - 2.1）和NZB浓度（0.01 - 0.42μg/ml）显示出明显的个体差异。未发现游离NZB、细胞结合NZB或AM表达水平与CSF T细胞比率之间存在相关性。在1例患者中观察到极低的NZB浓度和正常化的CSF T细胞比率。CSF CD8 T细胞的差异NZB饱和和AM表达可能导致它们在CSF中的相对富集。降低的CSF T细胞比率似乎对稳态NZB水平敏感，因为很快就发生了正常化。后者对于快速重建CNS免疫监视可能很重要。
