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Published on: September 4, 2017
Oligoclonal immune response in cerebral cavernous malformations. Laboratory investigation
Changbin Shi1, Robert Shenkar, H Hunt Batjer
1Department of Neurological Surgery, Evanston Northwestern Healthcare, Illinois 60201, USA.
Insights
Cerebral cavernous malformations (CCMs) show a unique, localized immune response. Immunoglobulin G (IgG) analysis revealed an oligoclonal pattern within CCM lesions, suggesting a specific B cell expansion.
Area of Science:
- Neuroimmunology
- Cerebrovascular Diseases
- Molecular Biology
Background:
- Cerebral cavernous malformations (CCMs) pathogenesis involves genetic factors, but immune responses may drive lesion progression.
- The unique environment within CCMs suggests a potential role for localized immune activity.
Purpose of the Study:
- To investigate the immunoglobulin (Ig) fraction within CCM lesions for evidence of an oligoclonal immune response.
- To compare the Ig profile of CCMs with paired patient sera and other cerebrovascular malformations.
Main Methods:
- Analysis of surgically excised CCM lesions, arteriovenous malformations (AVMs), and control brain specimens.
- Isoelectric focusing was used to assess immunoglobulin G (IgG) clonality in tissue extracts and patient sera.
Main Results:
- B cells and plasmacytes were detected in CCM lesions.
- Four out of five CCM extracts exhibited an oligoclonal IgG pattern, distinct from the polyclonal pattern in patient sera.
- Oligoclonal IgG was not observed in AVMs or control brain samples.
Conclusions:
- CCM lesions demonstrate selective IgG synthesis, indicating localized immune activity.
- The oligoclonal IgG pattern suggests clonal expansion of B cells and/or plasmacytes within CCMs.
- This localized immune response may be antigen-driven or serve as a marker for inflammation in CCMs.
Object:
Mechanisms of cerebral cavernous malformation (CCM) pathogenesis include genetic predisposition in some cases, but other factors are likely to be involved in lesion proliferation and clinical manifestations. Given the unique antigenic milieu of CCMs, there may be a characteristic immune response in these lesions. We hypothesize that the immunoglobulin (Ig) fraction in CCMs reflects an oligoclonal immune response not present in paired sera from the same patients or in other types of cerebrovascular malformations.
Methods:
Surgically excised lesions from five patients with CCMs, three patients with arteriovenous malformations (AVMs), and four normal brain control specimens obtained at autopsy were homogenized and extract tested for IgG clonality by isoelectric focusing in parallel with each patient's serum.
Results:
The authors detected B cells in all three lesions examined, and plasmacytes in two out of three lesions examined. Four of five extracts of homogenized CCMs showed an oligoclonal pattern of IgG distinct from the polyclonal pattern seen in those patients' sera. Immununoglobulin G oligoclonality was not seen in AVMs or control brain specimens.
Conclusions:
The results of isoelectric focusing studies showed that CCM lesions had oligoclonal patterns of IgG unrelated to peripheral blood contamination, indicating selective synthesis of IgG within the lesions. This finding probably reflects a clonal expansion of B cells and/or plasmacytes in CCMs, an event that might be antigen-driven or a potential marker of inflammation.
