title: CEACAM1 mediates B cell aggregation in central nervous system autoimmunity.
abstract: B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1(+) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain -3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease.
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Damiano M
authors.initials: DM
authors.lastname: Rovituso
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Scheffler
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Wunsch
authors.affiliation: Department of Neurology, University Hospitals of Würzburg, Würzburg, Germany.|Department of Neurology, University Hospitals of Würzburg, Würzburg, Germany.|University Hospital Essen, Department of Neurology, Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Department of Neurology, University Hospitals of Würzburg, Würzburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dörck
authors.affiliation: Department of Neurology, Caritas-Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Ulzheimer
authors.affiliation: Department of Neurology, Klinikum Augsburg, Augsburg, Germany.
authors.forename: Antonios
authors.initials: A
authors.lastname: Bayas
authors.affiliation: Department of Neurology, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules