PMID- 26498276
OWN - NLM
STAT- MEDLINE
DCOM- 20160906
LR  - 20181202
IS  - 1468-1331 (Electronic)
IS  - 1351-5101 (Linking)
VI  - 23
IP  - 1
DP  - 2016 Jan
TI  - Monitoring the John Cunningham virus throughout natalizumab treatment in multiple 
      sclerosis patients.
PG  - 182-9
LID - 10.1111/ene.12834 [doi]
AB  - BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) cases 
      have arisen amongst multiple sclerosis patients treated with natalizumab. Our 
      objective was to gain a better understanding of the mechanisms that underlie the 
      John Cunningham virus (JCV) infection which causes PML. METHODS: A study was made 
      of (i) the quarterly JCV DNA levels in peripheral blood mononuclear cells 
      (PBMCs), serum and urine samples in 100 multiple sclerosis patients during their 
      natalizumab treatment (3-39 months), (ii) the association between human leukocyte 
      antigen (HLA) class II and the previous viral detection and (iii) the 
      identification of the JCV variants in those patients suspected of having PML. 
      RESULTS: (i) JCV DNA in PBMCs and/or serum was detected in 23% of our cohort. 
      Patients with an intermittent JCV excretion in urine had a significant increase 
      of the viral load and prevalence in this compartment during natalizumab 
      treatment. (ii) The frequency of the DRB1*07/DQA1*02:01/DQB1*02:02 haplotype 
      tended to be higher in patients with detectable versus undetectable JCV DNA in 
      PBMCs (P(corrected) = 0.108). (iii) The variants in PBMCs and serum of the 
      non-PML patient matched the archetype. In the patient with non-fatal PML, the 
      archetype and the same neurotropic variant in PBMCs, serum and cerebrospinal 
      fluid was identified at the time PML was diagnosed, whereas in the patient with a 
      worse PML prognosis, four neurotropic variants in the three previous compartments 
      were found by the PML diagnosis. CONCLUSIONS: The detection of the neurotropic 
      variant in blood during natalizumab treatment could be critical in the prevention 
      of the development of severe PML, since this variant appears simultaneously with 
      the clinical symptoms of PML and mutates quickly.
CI  - (c) 2015 EAN.
FAU - Dominguez-Mozo, M I
AU  - Dominguez-Mozo MI
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Garcia-Montojo, M
AU  - Garcia-Montojo M
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Arias-Leal, A
AU  - Arias-Leal A
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Garcia-Martinez, A
AU  - Garcia-Martinez A
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Santiago, J L
AU  - Santiago JL
AD  - Department of Immunology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Casanova, I
AU  - Casanova I
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Galan, V
AU  - Galan V
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Arroyo, R
AU  - Arroyo R
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Fernandez-Arquero, M
AU  - Fernandez-Arquero M
AD  - Department of Immunology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
FAU - Alvarez-Lafuente, R
AU  - Alvarez-Lafuente R
AD  - Department of Neurology, Instituto de Investigacion Sanitaria del Hospital 
      Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain.
LA  - eng
SI  - GENBANK/AF044719
SI  - GENBANK/KM043580
SI  - GENBANK/KM043744
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151025
PL  - England
TA  - Eur J Neurol
JT  - European journal of neurology
JID - 9506311
RN  - 0 (DNA, Viral)
RN  - 0 (Immunologic Factors)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Adult
MH  - DNA, Viral/*blood/urine
MH  - Female
MH  - Humans
MH  - Immunologic Factors/adverse effects/*therapeutic use
MH  - *JC Virus
MH  - Leukoencephalopathy, Progressive Multifocal/*blood/urine/virology
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*blood/drug therapy/urine
MH  - Natalizumab/adverse effects/*therapeutic use
OTO - NOTNLM
OT  - JC virus
OT  - multiple sclerosis
OT  - natalizumab
OT  - progressive multifocal leukoencephalopathy
EDAT- 2015/10/27 06:00
MHDA- 2016/09/07 06:00
CRDT- 2015/10/27 06:00
PHST- 2015/03/09 00:00 [received]
PHST- 2015/08/04 00:00 [accepted]
PHST- 2015/10/27 06:00 [entrez]
PHST- 2015/10/27 06:00 [pubmed]
PHST- 2016/09/07 06:00 [medline]
AID - 10.1111/ene.12834 [doi]
PST - ppublish
SO  - Eur J Neurol. 2016 Jan;23(1):182-9. doi: 10.1111/ene.12834. Epub 2015 Oct 25.