Stüve Olaf, Marra Christina M, Jerome Keith R, Cook Linda, Cravens Petra D, Cepok Sabine, Frohman Elliot M, Phillips J Theodore, Arendt Gabriele, Hemmer Bernhard, Monson Nancy L, Racke Michael K
Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, USA.
Ann Neurol. 2006 May;59(5):743-7. doi: 10.1002/ana.20858.
Our objective was to test whether natalizumab, an antibody against very late activating antigen (VLA)-4, interferes with central nervous system immune surveillance as assessed by leukocyte cell numbers and cellular phenotypes in cerebrospinal fluid (CSF) and peripheral blood.
Cell numbers and cellular phenotypes in CSF and peripheral blood were analyzed in multiple sclerosis (MS) patients treated with natalizumab, untreated MS patients, and patients with other neurological disease (OND). JC virus DNA in the CSF and peripheral blood was quantified by kinetic polymerase chain reaction.
CSF leukocyte counts, CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD138(+) plasma cells were significantly lower in natalizumab-treated MS patients compared with OND patients and untreated MS patients. JC virus DNA was not detected in CSF or peripheral blood from natalizumab-treated patients. Six months after cessation of natalizumab therapy, low lymphocyte counts in the CSF persisted. The patient with the highest total leukocyte and CD4(+) and CD8(+)T-cell counts in the CSF experienced a clinical relapse.
These data suggest that natalizumab treatment results in a prolonged decrease of lymphocytes in the CSF and are consistent with the hypothesis that natalizumab impairs immune surveillance of the central nervous system.
我们的目的是测试那他珠单抗，一种抗极晚期活化抗原（VLA）-4的抗体，是否会干扰中枢神经系统免疫监测，这通过脑脊液（CSF）和外周血中的白细胞数量及细胞表型来评估。
对接受那他珠单抗治疗的多发性硬化症（MS）患者、未治疗的MS患者以及患有其他神经系统疾病（OND）的患者的CSF和外周血中的细胞数量及细胞表型进行分析。通过实时聚合酶链反应对CSF和外周血中的JC病毒DNA进行定量。
与OND患者和未治疗的MS患者相比，接受那他珠单抗治疗的MS患者的CSF白细胞计数、CD4(+)和CD8(+) T细胞、CD19(+) B细胞以及CD138(+)浆细胞显著降低。在接受那他珠单抗治疗的患者的CSF或外周血中未检测到JC病毒DNA。那他珠单抗治疗停止6个月后，CSF中的淋巴细胞计数仍维持在较低水平。CSF中白细胞总数以及CD4(+)和CD8(+) T细胞计数最高的患者出现了临床复发。
这些数据表明那他珠单抗治疗导致CSF中淋巴细胞数量长期减少，并且与那他珠单抗损害中枢神经系统免疫监测的假说一致。
