title: Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms.
abstract: Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138(+) plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1d(hi)CD5(+) regulatory B cells show resistance to depletion, and myelin-specific Foxp3(+) regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Monica
authors.initials: M
authors.lastname: Blazek
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Sara
authors.initials: S
authors.lastname: Ireland
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Sterling
authors.initials: S
authors.lastname: Ortega
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Anouk
authors.initials: A
authors.lastname: Meeuwissen
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
authors.forename: Ann
authors.initials: A
authors.lastname: Stowe
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878; and.
authors.forename: Laura
authors.initials: L
authors.lastname: Carter
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878; and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878; and.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390 nancy.monson@utsouthwestern.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D002470:Cell Survival; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D015202:Protein Engineering; D015398:Signal Transduction; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein