Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous
system (CNS). Natalizumab (®Tysabri) is a humanized recombinant monoclonal antibody
that binds to the alpha (α)4 chain of the α4 beta (β)1 integrin (very late activation antigen 4; VLA-4), and α4β7 integrin. Recently, two patients with MS and one patient with Crohn’s disease who
were treated with natalizumab in the setting of clinical trials developed progressive
multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with
the polyoma virus JC. We recently showed that natalizumab decreases the numbers of
CD4+ and CD8+ T lymphocytes, CD19+ B cells, and CD138+ plasma cells in the cerebrospinal fluid (CSF) of patients with MS on natalizumab
therapy. In addition, we demonstrated that the cell numbers in CSF remained unchanged
even 6 months after cessation of natalizumab treatment.
Keywords
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References
- Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri) in inflammatory diseases.CNS Drug Rev. 2007; 13: 79-95
- Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis.N Engl J Med. 2005; 353: 369-374
- Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.N Engl J Med. 2005; 353: 375-381
- Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease.N Engl J Med. 2005; 353: 362-368
- Immune surveillance in multiple sclerosis patients treated with natalizumab.Ann Neurol. 2006; 59: 743-747
- Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis.Arch Neurol. 2006; 63: 1383-1387
- Migration of hematogenous cells through the blood-brain barrier and the initiation of CNS inflammation.Brain Pathol. 1991; 1: 97-105
- Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis.Nat Med. 2005; 11: 328-334
- New diagnostic criteria for multiple sclerosis: guidelines for research protocols.Ann Neurol. 1983; 13: 227-231
- Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis.Arch Neurol. 2005; 62: 258-264
- Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis.Brain. 2001; 124: 2169-2176
- T-cell subsets in multiple sclerosis: relationships between peripheral blood and cerebrospinal fluid.Acta Neurol Scand. 1985; 71: 242-248
- T-cell subsets in the cerebrospinal fluid and blood of patients with multiple sclerosis.J Neuroimmunol. 1988; 20: 229-232
- The imbalance in CSF T cell subsets in active multiple sclerosis.Acta Neurol Scand. 1988; 77: 202-209
- T-cell phenotypic profiles in the cerebrospinal fluid and peripheral blood of multiple sclerosis patients.J Neurol Sci. 1992; 108: 93-98
- Natalizumab effects on immune cell responses in multiple sclerosis.Ann Neurol. 2006; 59: 748-754
Article info
Publication history
Accepted:
March 28,
2008
Received in revised form:
March 25,
2008
Received:
January 29,
2008
Identification
Copyright
Published by Elsevier Inc.
