title: Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis.
abstract: OBJECTIVE
  To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment.
  
  
  METHODS
  Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined.
  
  
  RESULTS
  In comparison to CD4+T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56brightNK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change.
  
  
  CONCLUSIONS
  Our findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56brightNK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56brightNK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS.
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Ahmetspahic
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulte-Mecklenbeck
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwarte
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Jörgens
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scheu
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Windhagen
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Graefe
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Melzer
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of Neurology (C.C.G., T.R., A.S.-M., N.M., L.K., H.W., S.G.M.), University Hospital Münster; Department of Psychiatry (D.A., K.S., S.J., V.A., J.A.) and Cluster of Excellence EXC 1003, Cells in Motion (D.A., K.S., H.W., S.G.M.), University of Münster; Institute of Medical Microbiology and Hospital Hygiene (S.S.), University of Düsseldorf; and Department of Neurology (S.W., B.G.), Clinics Osnabrück, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Alferink