Stüve Olaf, Marra Christina M, Bar-Or Amit, Niino Masaaki, Cravens Petra D, Cepok Sabine, Frohman Elliot M, Phillips J Theodore, Arendt Gabriele, Jerome Keith R, Cook Linda, Grand'Maison Francois, Hemmer Bernhard, Monson Nancy L, Racke Michael K
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, USA.
Arch Neurol. 2006 Oct;63(10):1383-7. doi: 10.1001/archneur.63.10.1383.
Treatment with natalizumab, a monoclonal antibody against the adhesion molecule very late activation antigen 4, an alpha4beta(1) integrin, was recently associated with the development of progressive multifocal leukoencephalopathy, a demyelinating disorder of the central nervous system caused by JC virus infection.
To test the effect of natalizumab treatment on the CD4(+)/CD8(+) T-cell ratios in cerebrospinal fluid (CSF) and peripheral blood.
Prospective longitudinal study.
Academic and private multiple sclerosis centers.
Patients with multiple sclerosis (MS) treated with natalizumab, untreated patients with MS, patients with other neurologic diseases, and human immunodeficiency virus-infected patients.
CD4(+) and CD8(+) T cells were enumerated in CSF and peripheral blood. The mean fluorescence intensity of unbound alpha4 integrin on peripheral blood CD4(+) and CD8(+) T cells was analyzed before and after natalizumab therapy.
Natalizumab therapy decreased the CSF CD4(+)/CD8(+) ratio of patients with MS to levels similar to those of human immunodeficiency virus-infected patients. CD4(+)/CD8(+) ratios in peripheral blood in patients with MS progressively decreased with the number of natalizumab doses, but they remained within normal limits. Six months after the cessation of natalizumab therapy, CSF CD4(+)/CD8(+) ratios normalized. The expression of unbound alpha4 integrin on peripheral blood T cells decreases with natalizumab therapy and was significantly lower on CD4(+) vs CD8(+) T cells.
Natalizumab treatment alters the CSF CD4(+)/CD8(+) ratio. Lower expression of unbound alpha4 integrin on CD4(+) T cells is one possible mechanism. These results may have implications for the observation that some natalizumab-treated patients with MS developed progressive multifocal leukoencephalopathy.
那他珠单抗是一种针对黏附分子极迟活化抗原4（一种α4β1整合素）的单克隆抗体，近期研究发现其治疗与进行性多灶性白质脑病的发生有关，这是一种由JC病毒感染引起的中枢神经系统脱髓鞘疾病。
检测那他珠单抗治疗对脑脊液（CSF）和外周血中CD4⁺/CD8⁺T细胞比例的影响。
前瞻性纵向研究。
学术及私立多发性硬化症中心。
接受那他珠单抗治疗的多发性硬化症（MS）患者、未接受治疗的MS患者、其他神经系统疾病患者以及人类免疫缺陷病毒感染患者。
对CSF和外周血中的CD4⁺和CD8⁺T细胞进行计数。分析那他珠单抗治疗前后外周血CD4⁺和CD8⁺T细胞上未结合的α4整合素的平均荧光强度。
那他珠单抗治疗使MS患者的CSF CD4⁺/CD8⁺比例降至与人类免疫缺陷病毒感染患者相似的水平。MS患者外周血中的CD4⁺/CD8⁺比例随那他珠单抗剂量的增加而逐渐降低，但仍在正常范围内。那他珠单抗治疗停止6个月后，CSF CD4⁺/CD8⁺比例恢复正常。那他珠单抗治疗后外周血T细胞上未结合的α4整合素表达降低，且CD4⁺T细胞上的表达明显低于CD8⁺T细胞。
那他珠单抗治疗可改变CSF CD4⁺/CD8⁺比例。CD4⁺T细胞上未结合的α4整合素表达降低可能是一种机制。这些结果可能与部分接受那他珠单抗治疗的MS患者发生进行性多灶性白质脑病的观察结果有关。
