PMID- 24049136
OWN - NLM
STAT- MEDLINE
DCOM- 20140512
LR  - 20151119
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 81
IP  - 16
DP  - 2013 Oct 15
TI  - Natalizumab affects the T-cell receptor repertoire in patients with multiple 
      sclerosis.
PG  - 1400-8
LID - 10.1212/WNL.0b013e3182a84101 [doi]
AB  - OBJECTIVE: To assess changes in the T-cell receptor (TCR) repertoire in 
      peripheral venous blood and CSF of patients with multiple sclerosis (MS) treated 
      with natalizumab and the potential implication for developing progressive 
      multifocal leukoencephalopathy (PML) and PML-immune reconstitution inflammatory 
      syndrome (IRIS). METHODS: The TCR repertoire in blood and CSF was assessed by 
      complementarity determining region 3 spectratyping in 59 patients with MS treated 
      with natalizumab for at least 18 months, 5 cases of natalizumab-associated PML, 
      17 age- and sex-matched patients with MS not treated with natalizumab, and 12 
      healthy controls. RESULTS: Patients with MS presented with peripheral TCR 
      repertoire expansions in blood, which appeared less prominent during therapy with 
      natalizumab. TCR repertoire restrictions observed in CSF were most pronounced in 
      patients with MS treated with natalizumab. In patients who developed PML with 
      longitudinal samples available, new identical TCR receptor length expansions in 
      blood and CSF were observed following plasma exchange, and preceded the 
      development of IRIS. CONCLUSIONS: Profound TCR repertoire restrictions in CSF of 
      patients treated with natalizumab reflect an altered immune surveillance of the 
      CNS, which may contribute to an increased risk of developing PML. Natalizumab 
      seems to prompt an impaired or delayed peripheral expansion of antigen-specific T 
      cells, whereas increased reconstitution of peripheral T-cell expansion following 
      plasma exchange may trigger PML-IRIS. Our data suggest that treatment with 
      natalizumab results in broader changes in the T-cell immune repertoire beyond 
      lymphocyte migration.
FAU - Warnke, Clemens
AU  - Warnke C
AD  - From the Department of Neurology (C.W., A.K.M., M.S., T.D., L.N., G.M.z.H., 
      H.-P.H., B.C.K.) and Institute for Virology (O.A.), Medical Faculty, 
      Heinrich-Heine-University, Dusseldorf, Germany; and the Department of Clinical 
      Neuroscience (C.W., A.F.-H.), Karolinska Institutet, Stockholm, Sweden.
FAU - Mausberg, Anne K
AU  - Mausberg AK
FAU - Stettner, Mark
AU  - Stettner M
FAU - Dehmel, Thomas
AU  - Dehmel T
FAU - Nekrich, Lina
AU  - Nekrich L
FAU - Meyer zu Horste, Gerd
AU  - Meyer zu Horste G
FAU - Hartung, Hans-Peter
AU  - Hartung HP
FAU - Fogdell-Hahn, Anna
AU  - Fogdell-Hahn A
FAU - Adams, Ortwin
AU  - Adams O
FAU - Kieseier, Bernd C
AU  - Kieseier BC
LA  - eng
PT  - Journal Article
DEP - 20130918
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
CIN - Neurology. 2013 Oct 15;81(16):1372-3. PMID: 24049137
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects
MH  - Female
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/diagnosis/etiology
MH  - Leukoencephalopathy, Progressive Multifocal/*chemically induced/diagnosis
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/blood/cerebrospinal fluid/*immunology
MH  - Natalizumab
MH  - Plasma Exchange/adverse effects
MH  - Receptors, Antigen, T-Cell/*biosynthesis
MH  - Young Adult
EDAT- 2013/09/21 06:00
MHDA- 2014/05/13 06:00
CRDT- 2013/09/20 06:00
PHST- 2013/09/20 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2014/05/13 06:00 [medline]
AID - WNL.0b013e3182a84101 [pii]
AID - 10.1212/WNL.0b013e3182a84101 [doi]
PST - ppublish
SO  - Neurology. 2013 Oct 15;81(16):1400-8. doi: 10.1212/WNL.0b013e3182a84101. Epub 
      2013 Sep 18.