Immune complex formation and in situ B-cell clonal expansion in human cerebral cavernous malformations

J Neuroimmunol. 2014 Jul 15;272(1-2):67-75. doi: 10.1016/j.jneuroim.2014.04.016. Epub 2014 May 10.


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.

Keywords: Antibody; Antigen; Cerebral cavernous malformations; Clonal expansion; IgG; Lymphocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Complex / immunology*
  • Antigens, CD / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Cell Proliferation
  • Female
  • Hemangioma, Cavernous, Central Nervous System / immunology*
  • Hemangioma, Cavernous, Central Nervous System / pathology*
  • Humans
  • Laser Capture Microdissection
  • Male
  • Single-Chain Antibodies / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology


  • Antigen-Antibody Complex
  • Antigens, CD
  • Single-Chain Antibodies