title: Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment.
abstract: OBJECTIVE
  Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity.
  
  
  METHODS
  Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients ( n = 33), untreated RRMS patients ( n = 13), and healthy controls ( n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients.
  
  
  RESULTS
  Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-γ+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed.
  
  
  CONCLUSIONS
  Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug's mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bühler
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Fleischer
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Luessi
authors.affiliation: Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Ayman
authors.initials: A
authors.lastname: Rezk
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Belikan
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Graetz
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Gollan
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Wolf
authors.affiliation: Department of Nephrology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Lutz
authors.affiliation: Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany/Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.affiliation: Focus Program Translational Neurosciences (FTN), Rhine-Main Neuroscience Network (rmn2), Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D000069442:Natalizumab
keywords: Multiple sclerosis; interleukin-17; lymphocytes; magnetic resonance imaging; natalizumab