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• W1974024509 abstract "Cerebral cavernous malformations (CCMs) affect more than one million Americans, predisposing them to a lifetime risk of hemorrhagic stroke and epilepsy. A potential role of the immune response in this disease has not been postulated previously but is compelling given the unique antigenic milieu of CCM lesions with sequestered thrombi and a leaky blood-brain barrier and the numerous examples of immune modulation of angiogenesis in other disease states. The objective of this article is to reveal novel observations about apparent immune responses in CCM lesions excised from human patients and to outline the potential pathobiological significance of these observations, specific hypotheses for future research, and potential clinical implications.We reviewed data from differential gene expression revealing several immunoglobulin and other related genes markedly upregulated within human CCM lesions. Other observations are presented revealing infiltration of antibody-producing B lymphocytes and plasma cells in CCM lesions. We also present recent data demonstrating fivefold enrichment of gamma globulin to albumin ratio in a human lesion compared with serum from the same patient and oligoclonality of IgG in four of five CCM lesions, but not in paired sera from the same patients or in control specimens.We describe ongoing research aiming to characterize cellular and humoral components of the immune response in CCMs and initiating investigation into its clonality by isoelectric focusing on the predominant immunoglobulin isotypes isolated from the lesion, in comparison to the patient's serum, and by the distribution of lengths of complementary-determining region 3 of the immunoglobulin heavy chain genes in messenger ribonucleic acid isolated from lesions and from pooled plasma cells and B cells laser captured from CCMs in comparison to peripheral lymphocytes from the blood of the same patients.Immune response could play a role in or represent a potential marker of CCM lesion proliferation and hemorrhage or could otherwise contribute to lesion phenotype. The ongoing studies will generate preliminary data for future research aimed at comparing the immune response in quiescent versus clinically aggressive CCM lesions. An oligoclonal immune response shown in this research would stimulate future experiments to identify autoimmune or extrinsic antigenic triggers involved in CCM disease." @default.
• W1974024509 created "2016-06-24" @default.
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• W1974024509 date "2007-10-01" @default.
• W1974024509 modified "2023-09-28" @default.
• W1974024509 title "CONCEPTS AND HYPOTHESES" @default.
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• W1974024509 doi "https://doi.org/10.1227/01.neu.0000298897.38979.07" @default.
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