PMID- 21908480
OWN - NLM
STAT- MEDLINE
DCOM- 20120619
LR  - 20151119
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 18
IP  - 3
DP  - 2012 Mar
TI  - Immunological and clinical consequences of treating a patient with natalizumab.
PG  - 335-44
LID - 10.1177/1352458511421919 [doi]
AB  - BACKGROUND: Long-term therapy with natalizumab increases the risk of progressive 
      multifocal leukoencephalopathy (PML). OBJECTIVES: We present a patient study 
      through therapy, the diagnosis of PML (after 29 infusions), plasma exchange (PE) 
      and development of immune reconstitution inflammatory syndrome (IRIS). METHODS: 
      Routine diagnostics, magnetic resonance imaging (MRI), immunological status (flow 
      cytometry, T-cell migration assays and T-cell repertoire analysis), and brain 
      biopsy with immunohistological analysis. RESULTS: CD49d decreased after 12 months 
      of treatment. At PML diagnosis, CD49d expression and migratory capacity of T 
      cells was low and peripheral T-cell receptor (TCR) complexity showed severe 
      perturbations. The distribution of peripheral monocytes changed from CCR5+ to 
      CCR7+. After PE some changes reverted: CD49d increased and overshot earliest 
      levels, migratory capacities of T cells recovered and peripheral TCR complexity 
      increased. With no clinical, routine laboratory or cerebrospinal fluid (CSF) 
      changes, MRI 2 months after PE demonstrated progressive lesion development. Brain 
      histopathology confirmed the presence of infiltrates indicative of IRIS without 
      clinical signs, immunologically accompanied by CCR7/CCR5 recovery of peripheral 
      monocytes. CONCLUSION: Natalizumab-associated immunological changes accompanying 
      PML were reversible after PE; IRIS can occur very late, remain asymptomatic and 
      be elusive to CSF analysis. Our study may provide insights into the changes under 
      treatment with natalizumab associated with JC virus control.
FAU - Schwab, Nicholas
AU  - Schwab N
AD  - Department of Neurology-Inflammatory Disorders of the Nervous System and 
      Neurooncology, University of Munster, Munster, Germany.
FAU - Hohn, Karin G
AU  - Hohn KG
FAU - Schneider-Hohendorf, Tilman
AU  - Schneider-Hohendorf T
FAU - Metz, Imke
AU  - Metz I
FAU - Stenner, Max-Philipp
AU  - Stenner MP
FAU - Jilek, Samantha
AU  - Jilek S
FAU - Du Pasquier, Renaud A
AU  - Du Pasquier RA
FAU - Gold, Ralf
AU  - Gold R
FAU - Meuth, Sven G
AU  - Meuth SG
FAU - Ransohoff, Richard M
AU  - Ransohoff RM
FAU - Bruck, Wolfgang
AU  - Bruck W
FAU - Wiendl, Heinz
AU  - Wiendl H
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110909
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use
MH  - Brain/immunology/pathology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/immunology
MH  - JC Virus/immunology
MH  - Leukoencephalopathy, Progressive Multifocal/diagnosis/*etiology/immunology
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*complications/drug therapy/pathology
MH  - Natalizumab
MH  - Plasma Exchange
MH  - Treatment Outcome
EDAT- 2011/09/13 06:00
MHDA- 2012/06/20 06:00
CRDT- 2011/09/13 06:00
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/06/20 06:00 [medline]
AID - 1352458511421919 [pii]
AID - 10.1177/1352458511421919 [doi]
PST - ppublish
SO  - Mult Scler. 2012 Mar;18(3):335-44. doi: 10.1177/1352458511421919. Epub 2011 Sep 
      9.