Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias

Epilepsia. 2010 Sep;51(9):1763-73. doi: 10.1111/j.1528-1167.2010.02547.x.

Abstract

Purpose: Induction of inflammatory pathways has been reported in epileptic patients with focal malformations of cortical development. In the present study we examined the innate and adaptive immune responses in focal cortical dysplasia (FCD) with different histopathologic and pathogenetic features.

Methods: The inflammatory cell components and the induction of major proinflammatory pathways and molecules [complement pathway, interleukin (IL)-1β, and chemokine monocyte chemotactic protein-1 (MCP1)] was investigated in surgical specimens of sporadic type IA and type IIB FCD using immunocytochemical methods.

Results: FCD II but not FCD I cases exhibit activation of the mammalian target of rapamycin (mTOR) cascade with strong neuronal expression of the phosphorylated isoform of S6 protein. Microglia reactivity was increased in all lesions (FCD I and II) compared to control tissue; however, the number of HLA-DR-positive cells was significantly higher in FCD II than in FCD I. In FCD II specimens we also observed perivascular and parenchymal T lymphocytes (CD3(+) ), with a predominance of CD8(+) T-cytotoxic/suppressor lymphocytes, as well as a few dendritic cells. Expression of components of the complement cascade, IL-1β, and MCP1 was prominent in FCD II cases.

Discussion: Our findings indicate a prominent activation of both innate and adaptive immunity, with involvement of different inflammatory pathways in FCD II cases, supporting the possible involvement of inflammation in the epileptogenesis of these lesions, as well as the notion that FCD II is pathologically distinct from FCD I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Adaptive Immunity / physiology*
  • Cerebral Cortex / immunology
  • Cerebral Cortex / pathology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Complement Activation / genetics
  • Complement Activation / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Epilepsy / genetics
  • Epilepsy / immunology*
  • Epilepsy / pathology
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Immunity, Innate / physiology*
  • Immunohistochemistry
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Malformations of Cortical Development / genetics
  • Malformations of Cortical Development / immunology*
  • Malformations of Cortical Development / pathology
  • Microglia / immunology
  • Microglia / pathology
  • Neurons / immunology
  • Neurons / pathology
  • Neurons / physiology
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / immunology

Substances

  • Chemokine CCL2
  • Interleukin-1
  • Receptors, Metabotropic Glutamate