Immune surveillance in multiple sclerosis patients treated with natalizumab.

TitleImmune surveillance in multiple sclerosis patients treated with natalizumab.
Publication TypeJournal Article
Year of Publication2006
AuthorsStüve O, Marra CM, Jerome KR, Cook L, Cravens PD, Cepok S, Frohman EM, J Phillips T, Arendt G, Hemmer B, Monson NL, Racke MK
JournalAnn Neurol
Volume59
Issue5
Pagination743-7
Date Published2006 May
ISSN0364-5134
KeywordsAdult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antigens, CD19, B-Lymphocytes, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes, Cohort Studies, DNA, Viral, Female, Flow Cytometry, Humans, Immunologic Surveillance, Integrin alpha4beta1, JC Virus, Leukocyte Count, Lymphocyte Count, Male, Middle Aged, Multiple Sclerosis, Natalizumab, Nervous System Diseases, Neutralization Tests, Phenotype, Reverse Transcriptase Polymerase Chain Reaction
Abstract

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.

DOI10.1002/ana.20858
Alternate JournalAnn. Neurol.
PubMed ID16634029
Grant ListAI 27664 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
NS 37513 / NS / NINDS NIH HHS / United States
NS 40993 / NS / NINDS NIH HHS / United States
NS 44250 / NS / NINDS NIH HHS / United States