Immune Response in Human Cerebral Cavernous Malformations

Changbin Shi, Robert Shenkar, Hongyan Du, Edward Duckworth, Harish Raja, H. Hunt Batjer, Issam A. Awad

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background and Purpose-: Preliminary observations suggesting the presence of B and plasma cells and oligoclonality of immunoglobulin (Ig) G in cerebral cavernous malformations (CCM) have motivated a systematic study correlating the infiltration of the immune cells with clinical activity and antigen-triggered immune response in surgically excised lesions. Methods-: Infiltration of plasma, B, T, and human leukocyte antigen-DR-expressing cells and macrophages within 23 excised CCM was related to clinical activity. Relative amounts of Ig isotypes were determined. IgG clonality of mRNA from CCM was assessed by spectratyping, cloning, and sequencing. Results-: Infiltration of the immune cells ranged widely within CCM lesions, and cells were generally coexpressed with each other. Immune cell infiltration did not associate with recent bleeding and lesion growth. Significantly more B lymphocytes in CCM lesions were associated with venous anomaly. More T cells were present in solitary lesions. More T cells and less macrophages were present in CCM from younger subjects. IgG isotype was present in all CCM lesions. Most lesions also expressed IgM and IgA, with IgM predominance over IgA correlating with recent CCM growth. Oligoclonality was shown in IgG mRNA from CCM, but not from peripheral blood lymphocytes, with only 8 complementary-determining region 3 sequences observed among 134 clones from 2 CCM lesions. Conclusions-: An antigen-directed oligoclonal IgG immune response is present within CCM lesions regardless of recent clinical activity. Apparent differences in immune response in younger patients and in lesions with recent growth will need confirmation in other series. The pathogenicity of oligoclonal immune response will require systematic hypothesis testing in recently available CCM murine models.

Original languageEnglish (US)
Pages (from-to)1659-1665
Number of pages7
JournalStroke
Volume40
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Cerebral cavernous malformations
  • Immune response
  • Immunohistochemistry
  • Lymphocytes
  • Oligoclonality

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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  • Cite this

    Shi, C., Shenkar, R., Du, H., Duckworth, E., Raja, H., Batjer, H. H., & Awad, I. A. (2009). Immune Response in Human Cerebral Cavernous Malformations. Stroke, 40(5), 1659-1665. https://doi.org/10.1161/STROKEAHA.108.538769