Oligoclonal immune response in cerebral cavernous malformations

Shi, Changbin; Shenkar, Robert; Batjer, H. Hunt; Check, Irene J.; Awad, Issam A.

doi:10.3171/jns-07/11/1023

Cited by 37 publications

(27 citation statements)

References 15 publications

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“…Four of these lesions were also stained for plasma cells. The immunohistochemistry technique has been described previously (52) with preliminary observations on three of these cases (53). Antibodies were chosen because of experience with them in clinical pathology applications and their successful use in formalin-fixed, paraffin-embedded tissue.…”

Section: Methodsmentioning

confidence: 99%

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Concepts and Hypotheses

et al. 2007

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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.

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Section: Methodsmentioning

confidence: 99%

“…Our laboratory has recently demonstrated oligoclonality of IgG in CCM lesions surgically excised from four of five patients, but not in their paired sera nor in control specimens (53).…”

Section: Preliminary Findingsmentioning

confidence: 98%

Concepts and Hypotheses

et al. 2007

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“…ultrastructural analysis, however, has suggested that the Cm phenotype might be modulated by immune responses to hemorrhage or to other lesional elements, such as these cytoskeletal proteins. 55,56 studies have demonstrated the presence of oligoclonal igG bands that are distinct from those found in peripheral lymphocytes. [55][56][57] indeed, shi et al spectra typed, cloned and sequenced specific complementary determining region 3 (CDr3) sequences of genes encod ing igG heavy variable chains.…”

Section: Clinical Presentationmentioning

confidence: 99%

“…55,56 studies have demonstrated the presence of oligoclonal igG bands that are distinct from those found in peripheral lymphocytes. [55][56][57] indeed, shi et al spectra typed, cloned and sequenced specific complementary determining region 3 (CDr3) sequences of genes encod ing igG heavy variable chains. 57 these CDr3 sequences identify specific Bcell clonal origins and are specific for the antigen to which the igG binds.…”

Section: Clinical Presentationmentioning

confidence: 99%

Cavernous malformations: natural history, diagnosis and treatment

et al. 2009

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Cavernous malformations (CMs) consist of dilated vascular channels that have a characteristic appearance on MRI. CMs are usually found intracranially, although such lesions can also affect the spinal cord. Individuals with CMs can present with epilepsy and focal neurological deficits or acute intracranial hemorrhage. In many cases, however, patients with such lesions are asymptomatic at diagnosis. Furthermore, several natural history studies have documented that a substantial proportion of asymptomatic CMs follow a benign course. Surgical resection is recommended for CMs that require intervention. Radiosurgery has been advocated for many lesions that have not been easily accessible by conventional surgery. The outcomes of radiosurgery and surgery for deep lesions, however, vary widely between studies, rendering treatment recommendations for such CMs difficult to make. In addition to reviewing the literature, this article will discuss the current understanding of lesion pathophysiology and explore the controversial issues in the management of CMs, such as when to use radiosurgery or surgery in deep-seated lesions, the treatment of epilepsy, and the safety of anticoagulation.

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“…Human CCM lesions manifest a robust oligoclonal antigen-driven immune response (Shi et al, 2007(Shi et al, , 2009). Radiation exposure can also trigger de novo development of CCM lesions (Jain et al, 2005;Nyáry et al, 2007).…”

Section: Ccm2 Haploinsufficiency Induces Rock-mediated Vascular Leakmentioning

confidence: 99%

Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity

Stockton¹,

Shenkar²,

Awad³

et al. 2010

J Cell Biol

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, reversible by fasudil, a ROCK inhibitor. Furthermore, we show that ROCK hyperactivity occurs in sporadic and familial human CCM endothelium as judged by increased phosphorylation of myosin light chain. These data establish that KRIT1-CCM2 interaction regulates vascular barrier function by suppressing Rho/ROCK signaling and that this pathway is dysregulated in human CCM endothelium, and they suggest that fasudil could ameliorate both CCM disease and vascular leak.

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Oligoclonal immune response in cerebral cavernous malformations

Cited by 37 publications

References 15 publications

Concepts and Hypotheses

Concepts and Hypotheses

Cavernous malformations: natural history, diagnosis and treatment

Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity

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