Immune surveillance in multiple sclerosis patients treated with natalizumab
Article first published online: 21 APR 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 5, pages 743–747, May 2006
How to Cite
Stüve, O., Marra, C. M., Jerome, K. R., Cook, L., Cravens, P. D., Cepok, S., Frohman, E. M., Phillips, J. T., Arendt, G., Hemmer, B., Monson, N. L. and Racke, M. K. (2006), Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol., 59: 743–747. doi: 10.1002/ana.20858
- Issue published online: 21 APR 2006
- Article first published online: 21 APR 2006
- Manuscript Accepted: 11 MAR 2006
- Manuscript Revised: 10 MAR 2006
- Manuscript Received: 30 OCT 2005
- NIH (National Institute of Neurological Disorders and Stroke). Grant Numbers: NS 37513, NS 44250, NS 40993
- National Multiple Sclerosis Society. Grant Number: RG 2969-B-7
- Deutsche Forschungsgemeinschaft. Grant Numbers: He2386/4-1, He2386/4-2
- Adult AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases. Grant Numbers: AI 38858, AI 27664
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. Ann Neurol 2006;59:743–747