Immune surveillance in multiple sclerosis patients treated with natalizumab

Ann Neurol. 2006 May;59(5):743-7. doi: 10.1002/ana.20858.


Objective: 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.

Methods: 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.

Results: 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.

Interpretation: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD19
  • B-Lymphocytes / physiology
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / physiology
  • Cohort Studies
  • DNA, Viral / blood
  • DNA, Viral / cerebrospinal fluid
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Surveillance / drug effects*
  • Integrin alpha4beta1 / antagonists & inhibitors
  • Integrin alpha4beta1 / immunology
  • JC Virus / metabolism
  • Leukocyte Count
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / immunology*
  • Natalizumab
  • Nervous System Diseases / blood
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / immunology
  • Neutralization Tests
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD19
  • DNA, Viral
  • Integrin alpha4beta1
  • Natalizumab