title: Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells.
abstract: 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.
authors.affiliation: Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. spadaro_michela@yahoo.it.|AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. spadaro_michela@yahoo.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Spadaro
authors.affiliation: Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. marzia.caldano@gmail.com.|AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. marzia.caldano@gmail.com.
authors.forename: Marzia
authors.initials: M
authors.lastname: Caldano
authors.affiliation: Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. fabiana.marnetto@gmail.com.|AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. fabiana.marnetto@gmail.com.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marnetto
authors.affiliation: Department Neuroscience, Imaging and Clinical Sciences, University 'G. d'Annunzio', Chieti, Italy. lugaresi@unich.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.affiliation: Clinical Neurobiology Unit Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. antonio.bertolotto@gmail.com.|AOU S. Luigi Gonzaga, Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), Regione Gonzole 10, 10043, Orbassano, Turin, Italy. antonio.bertolotto@gmail.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D000068717:Glatiramer Acetate / Q000494:pharmacology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D019041:L-Selectin / Q000096:biosynthesis*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009103:Multiple Sclerosis / Q000188:drug therapy; D000069442:Natalizumab / Q000494:pharmacology*; D000069283:Rituximab / Q000494:pharmacology; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab; D019041:L-Selectin; D000069283:Rituximab; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride