Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis.

TitleAltered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis.
Publication TypeJournal Article
Year of Publication2006
AuthorsStüve O, Marra CM, Bar-Or A, Niino M, Cravens PD, Cepok S, Frohman EM, J Phillips T, Arendt G, Jerome KR, Cook L, Grand'Maison F, Hemmer B, Monson NL, Racke MK
JournalArch Neurol
Volume63
Issue10
Pagination1383-7
Date Published2006 Oct
ISSN0003-9942
KeywordsAdolescent, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cohort Studies, Female, HIV Infections, Humans, Immunosuppression, Integrin alpha4beta1, Leukoencephalopathy, Progressive Multifocal, Longitudinal Studies, Male, Middle Aged, Multiple Sclerosis, Natalizumab, Prospective Studies
Abstract

BACKGROUND: 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.

OBJECTIVE: To test the effect of natalizumab treatment on the CD4(+)/CD8(+) T-cell ratios in cerebrospinal fluid (CSF) and peripheral blood.

DESIGN: Prospective longitudinal study.

SETTING: Academic and private multiple sclerosis centers.

PATIENTS: Patients with multiple sclerosis (MS) treated with natalizumab, untreated patients with MS, patients with other neurologic diseases, and human immunodeficiency virus-infected patients.

MAIN OUTCOME MEASURES: 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.

RESULTS: 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.

CONCLUSIONS: 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.

DOI10.1001/archneur.63.10.1383
Alternate JournalArch. Neurol.
PubMed ID17030653
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