Immune surveillance in multiple sclerosis patients treated with natalizumab.
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.


CONCLUSIONS
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.
Stüve
Olaf
O
Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, USA. olaf.stuve@utsouthwestern.edu
Marra
Christina M
CM
Jerome
Keith R
KR
Cook
Linda
L
Cravens
Petra D
PD
Cepok
Sabine
S
Frohman
Elliot M
EM
Phillips
J Theodore
JT
Arendt
Gabriele
G
Hemmer
Bernhard
B
Monson
Nancy L
NL
Racke
Michael K
MK
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000502:physiology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007157:Immunologic Surveillance / Q000187:drug effects*; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000276:immunology; D007577:JC Virus / Q000378:metabolism; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D000069442:Natalizumab; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D009500:Neutralization Tests; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D004279:DNA, Viral; D039041:Integrin alpha4beta1; D000069442:Natalizumab