Zimmer, TS;
Broekaart, DWM;
Luinenburg, M;
Mijnsbergen, C;
Anink, JJ;
Sim, NS;
Michailidou, I;
... Aronica, E; + view all
(2021)
Balloon cells promote immune system activation in focal cortical dysplasia type 2b.
Neuropathology and Applied Neurobiology
, 47
(6)
pp. 826-839.
10.1111/nan.12736.
Preview |
Text
Mills_nan.12736.pdf - Published Version Download (3MB) | Preview |
Abstract
AIMS: Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the mammalian target of rapamycin (mTOR) pathway. Histopathologically, FCD 2 is subdivided into FCD 2a and FCD 2b, the only discriminator being the presence of balloon cells (BCs) in FCD 2b. While pro-epileptogenic immune system activation and inflammatory responses are commonly detected in both subtypes, it is unknown what contextual role BCs play. METHODS: The present study employed RNA sequencing of surgically resected brain tissue from FCD 2a (n = 11) and FCD 2b (n = 20) patients compared to autopsy control (n = 9) focusing on three immune system processes: adaptive immunity, innate immunity and cytokine production. This analysis was followed by immunohistochemistry on a clinically well-characterised FCD 2 cohort. RESULTS: Differential expression analysis revealed stronger expression of components of innate immunity, adaptive immunity and cytokine production in FCD 2b than in FCD 2a, particularly complement activation and antigen presentation. Immunohistochemical analysis confirmed these findings, with strong expression of leukocyte antigen I and II in FCD 2b as compared to FCD 2a. Moreover, T-lymphocyte tissue infiltration was elevated in FCD 2b. Expression of markers of immune system activation in FCD 2b was concentrated in subcortical white matter. Lastly, antigen presentation was strongly correlated with BC load in FCD 2b lesions. CONCLUSIONS: We conclude that, next to mutation-driven mTOR activation and seizure activity, BCs are crucial drivers of inflammation in FCD 2b. Our findings indicate that therapies targeting inflammation may be beneficial in FCD 2b.
| Type: | Article |
|---|---|
| Title: | Balloon cells promote immune system activation in focal cortical dysplasia type 2b |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/nan.12736 |
| Publisher version: | https://doi.org/10.1111/nan.12736 |
| Language: | English |
| Additional information: | © 2021 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | balloon cells, focal cortical dysplasia, immune system, inflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10139406 |
Archive Staff Only
 |
View Item |
