title: Immune complex formation and in situ B-cell clonal expansion in human cerebral cavernous malformations.
abstract: Cerebral cavernous malformations (CCMs) represent clusters of dilated vascular channels, predisposing to hemorrhagic stroke and seizures. They are associated with defective blood brain barrier, hemorrhages of different ages and a robust inflammatory cell infiltrate. We report for the first time evidence of co-localized IgG and complement membrane attack complexes in CCM lesions. CD4(+) and CD8(+) T-cells are aggregated with CD20(+) B-cells. And IgG repertoire analyses demonstrate in situ B-cell clonal expansion and antigen-driven affinity maturation in CCMs. These results suggest an organ-intrinsic adaptive immune response in CCMs that should be further characterized as a potential therapeutic target.
authors.affiliation: Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Changbin
authors.initials: C
authors.lastname: Shi
authors.affiliation: Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Shenkar
authors.affiliation: Section of Rheumatology, Department of Medicine and The Knapp Center for Lupus and Immunology Research, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kinloch
authors.affiliation: Section of Rheumatology, Department of Medicine and The Knapp Center for Lupus and Immunology Research, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Henderson
authors.affiliation: Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Shaaya
authors.affiliation: Section of Transplantation, Department of Surgery, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
authors.affiliation: Section of Rheumatology, Department of Medicine and The Knapp Center for Lupus and Immunology Research, University of Chicago Medicine and Biological Sciences, USA.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
authors.affiliation: Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago Medicine and Biological Sciences, USA. Electronic address: iawad@uchicago.edu.
authors.forename: Issam A
authors.initials: IA
authors.lastname: Awad
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D057127:Single-Chain Antibodies / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D057127:Single-Chain Antibodies
keywords: Antibody; Antigen; Cerebral cavernous malformations; Clonal expansion; IgG; Lymphocyte