PMID- 26259673
OWN - NLM
STAT- MEDLINE
DCOM- 20160322
LR  - 20220321
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 12
DP  - 2015 Aug 12
TI  - Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells.
PG  - 146
LID - 10.1186/s12974-015-0365-x [doi]
LID - 146
AB  - BACKGROUND: The purpose of this research was to validate the low expression of 
      L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in 
      rolling and transmigration of leukocyte cells. A correlation between CD62LCD4+ T 
      cells low expression and progressive multifocal leukoencephalopathy (PML) 
      development has been suggested in multiple sclerosis (MS) patients treated with 
      NTZ. METHODS: We performed a flow cytometric analysis on peripheral blood 
      mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS 
      patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta 
      (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab 
      (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory 
      syndrome) patients and four longitudinal samples of a NTZ-treated patients before 
      and during the development of a clinical asymptomatic magnetic resonance imaging 
      (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. 
      Thirty-five NTZ-treated patients were studied longitudinally with three samples 
      taken 4 months apart. RESULTS: The NTZ-treated patients showed a lower percentage 
      of CD62L (33.68%, n = 113) than first-line treated patients (44.24%, n = 52, 
      p = 0.0004). NTZ effect was already clear during the first year of treatment 
      (34.68 ; p = 0.0184); it persisted in the following years and disappeared after 
      drug withdrawal (44.08%). Three percent of longitudinally analysed patients 
      showed a percentage of CD62LCD4+ T cells under a hypothetical threshold and one 
      patient with asymptomatic PML belongs to a group which expressed low percentage 
      of CD62LCD4+ T cells. CONCLUSIONS: Our research confirms that NTZ has a specific 
      effect on CD62LCD4+ T cells consisting in decreasing of the number of positive 
      cells. The low level of CD62L found in a clinically asymptomatic PML patient 
      strengthens its potential usefulness as a biomarker of high PML risk in 
      NTZ-treated patients. A larger study is required to better confirm the data.
FAU - Spadaro, Michela
AU  - Spadaro M
AD  - Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), 
      Regione Gonzole 10, 10043, Orbassano, Turin, Italy. spadaro_michela@yahoo.it.
AD  - AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi 
      Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. 
      spadaro_michela@yahoo.it.
FAU - Caldano, Marzia
AU  - Caldano M
AD  - Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), 
      Regione Gonzole 10, 10043, Orbassano, Turin, Italy. marzia.caldano@gmail.com.
AD  - AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi 
      Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. 
      marzia.caldano@gmail.com.
FAU - Marnetto, Fabiana
AU  - Marnetto F
AD  - Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), 
      Regione Gonzole 10, 10043, Orbassano, Turin, Italy. fabiana.marnetto@gmail.com.
AD  - AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi 
      Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. 
      fabiana.marnetto@gmail.com.
FAU - Lugaresi, Alessandra
AU  - Lugaresi A
AD  - Department Neuroscience, Imaging and Clinical Sciences, University 'G. 
      d'Annunzio', Chieti, Italy. lugaresi@unich.it.
FAU - Bertolotto, Antonio
AU  - Bertolotto A
AD  - Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), 
      Regione Gonzole 10, 10043, Orbassano, Turin, Italy. antonio.bertolotto@gmail.com.
AD  - AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi 
      Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. 
      antonio.bertolotto@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150812
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Immunologic Factors)
RN  - 0 (Natalizumab)
RN  - 126880-86-2 (L-Selectin)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 5M691HL4BO (Glatiramer Acetate)
RN  - 77238-31-4 (Interferon-beta)
RN  - G926EC510T (Fingolimod Hydrochloride)
SB  - IM
MH  - Adult
MH  - Aged
MH  - CD4-Positive T-Lymphocytes/drug effects/*metabolism
MH  - Female
MH  - Fingolimod Hydrochloride/pharmacology
MH  - Glatiramer Acetate/pharmacology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/cerebrospinal fluid/drug 
      therapy/immunology
MH  - Immunologic Factors/*pharmacology
MH  - Interferon-beta/pharmacology
MH  - L-Selectin/*biosynthesis
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects
MH  - Multiple Sclerosis/drug therapy
MH  - Natalizumab/*pharmacology
MH  - Rituximab/pharmacology
MH  - Young Adult
PMC - PMC4532246
EDAT- 2015/08/12 06:00
MHDA- 2016/03/24 06:00
PMCR- 2015/08/12
CRDT- 2015/08/12 06:00
PHST- 2015/02/20 00:00 [received]
PHST- 2015/07/21 00:00 [accepted]
PHST- 2015/08/12 06:00 [entrez]
PHST- 2015/08/12 06:00 [pubmed]
PHST- 2016/03/24 06:00 [medline]
PHST- 2015/08/12 00:00 [pmc-release]
AID - 10.1186/s12974-015-0365-x [pii]
AID - 365 [pii]
AID - 10.1186/s12974-015-0365-x [doi]
PST - epublish
SO  - J Neuroinflammation. 2015 Aug 12;12:146. doi: 10.1186/s12974-015-0365-x.