Balloon cells promote immune system activation in focal cortical dysplasia type 2b. Academic Article uri icon

Overview

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. CONCLUSION: 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.

authors

  • Zimmer, Till
  • Broekaart, Diede W M
  • Luinenburg, Mark
  • Mijnsbergen, Caroline
  • Anink, Jasper J
  • Sim, Nam Suk
  • Michailidou, Iliana
  • Jansen, Floor E
  • van Rijen, Peter C
  • Lee, Jeong Ho
  • François, Liesbeth
  • van Eyll, Jonathan
  • Dedeurwaerdere, Stefanie
  • van Vliet, Erwin A
  • Mühlebner, Angelika
  • Mills, James D
  • Aronica, Eleonora

publication date

  • June 8, 2021

Research

keywords

  • Epilepsy
  • Immune System
  • Malformations of Cortical Development
  • Malformations of Cortical Development, Group I
  • TOR Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC8518746

Scopus Document Identifier

  • 85107551902

Digital Object Identifier (DOI)

  • 10.1111/nan.12715

PubMed ID

  • 34003514

Additional Document Info

volume

  • 47

issue

  • 6