title: Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations.
abstract: OBJECTIVE
  We undertook a systems immunology approach of the adaptive immune system in multiple sclerosis (MS), overcoming tradeoffs between scale and level of detail, in order to identify the immunologic signature of MS and the changes wrought by current immunomodulatory treatments.
  
  
  METHODS
  We developed a comprehensive flow cytometry platform measuring 38 immunologic cell types in the peripheral blood of 245 individuals in a routine clinical setting. These include patients with MS, untreated or receiving any of 4 current immunomodulatory treatments (interferon-β, glatiramer acetate, natalizumab, or fingolimod), patients with autoimmune thyroid disease, and healthy controls.
  
  
  RESULTS
  An increase in memory CD8(+) T cells and B cells was observed in untreated patients with MS. Interferon-β and fingolimod induce significant changes upon multiple aspects of the peripheral immune system, with an unexpectedly prominent alteration of B cells. Overall, both treatments push the immune system in different directions, with only 2 significant effects shared across these treatments-an increase in transitional B cells and a decrease in class-switched B cells. We further identified heightened B cell-activating factor (BAFF) levels as regulating this shared B cell pathway.
  
  
  CONCLUSIONS
  A systems immunology approach established different immunologic profiles induced by current immunomodulatory MS treatments, offering perspectives for personalized medicine. Pathways shared between the immunologic architecture of existing efficacious treatments identify targets for future treatment design.
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Ine
authors.initials: I
authors.lastname: Pauwels
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Dean
authors.initials: D
authors.lastname: Franckaert
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Ide
authors.initials: I
authors.lastname: Smets
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Josselyn E
authors.initials: JE
authors.lastname: Garcia-Perez
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hilven
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Dina
authors.initials: D
authors.lastname: Danso-Abeam
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Joanne
authors.initials: J
authors.lastname: Terbeek
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Anh T L
authors.initials: AT
authors.lastname: Nguyen
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: De Muynck
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Decallonne
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dubois
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.affiliation: Department of Immunology and Microbiology (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), Laboratory for Neuroimmunology, Department of Neurosciences (I.P., I.S., K.H., B. Dubois, A.G.), Laboratory for Neurobiology, Department of Neurosciences (L.D.M.), Laboratory for Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine (B. Decallonne), and Department of Neurology, University Hospitals Leuven (I.S., J.T., B. Dubois), KU Leuven-University of Leuven; and Center for the Biology of Disease (J.D., D.F., J.E.G.-P., D.D.-A., A.T.L.N., A.L.), VIB (L.D.M.), Leuven, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Goris