title: Natalizumab treatment alters the expression of T-cell trafficking marker LFA-1 α-chain (CD11a) in MS patients.
abstract: To determine the long-term effect of natalizumab (NTZ) treatment on the expression of integrins and chemokine receptors involved in the migration of T cells towards the central nervous system (CNS).
  
  
  
  We drew the blood of 23 patients just before starting NTZ therapy and every 12 months thereafter, for up to 48 months of treatment. We assessed the ex-vivo expression of phenotype markers (CCR7 and CD45RA), CNS-addressing integrins (CD11a, CD49d and CD29) and chemokine receptors (CXCR3 and CCR6) in CD4+ or CD8+ T-cell subsets by flow cytometry.
  
  
  
  As compared to the pre-NTZ values, there was a marked increase in central memory (CCR7+/CD45RA-) CD4+ T cells and in effector memory (CCR7-/CD45RA-) CD8+ T cells at 12 and 24 months. In addition to an expected downregulation of both VLA-4 subunits (CD49d/CD29), we also found decreased T-cell expression of CXCR3 at 12 months, and of CD11a (LFA-1 αL subunit) at 12 months, but mostly at 24 months of NTZ treatment.
  
  
  
  Our data show a nadir of CD11a expression at 2 years of NTZ treatment, at the peak of incidence of progressive multifocal leukoencephalopathy (PML), indirectly suggesting that a lack of these molecules may play a role in the onset of PML in NTZ-treated patients.
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jilek
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Mathias
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Canales
authors.affiliation: Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lysandropoulos
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.affiliation: Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Renaud.Du-Pasquier@chuv.ch.
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D040881:CD11a Antigen / Q000097:blood* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D039041:Integrin alpha4beta1 / Q000097:blood / Q000276:immunology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood / Q000139:chemically induced / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab / Q000009:adverse effects / Q000627:therapeutic use*; D054399:Receptors, CCR6 / Q000097:blood / Q000276:immunology; D054367:Receptors, CXCR3 / Q000097:blood / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C106311:CCR6 protein, human; D040881:CD11a Antigen; C515187:CXCR3 protein, human; D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D000069442:Natalizumab; D054399:Receptors, CCR6; D054367:Receptors, CXCR3
keywords: Adverse effects; CD11a; CXCR3; LFA-1; T cell; VLA-4; cellular immunity; integrins; longitudinal study; natalizumab; progressive multifocal encephalopathy