LGI1 tumor tissue expression and serum autoantibodies in patients with primary malignant glioma

Clin Neurol Neurosurg. 2018 Jul:170:27-33. doi: 10.1016/j.clineuro.2018.04.010. Epub 2018 Apr 14.

Abstract

Objectives: The Leucine-rich glioma inactivated 1 (LGI1) protein is thought to be implicated in malignant progression of glioma tumors, and mutations in the encoding gene, LGI1, cause autosomal dominant lateral temporal epilepsy, a genetic focal epilepsy syndrome. The aim of this study was to investigate the possible involvement of LGI1 in high-grade glioma-associated epilepsy by analyzing its expression in tumor specimens of patients with and without epilepsy and by searching for LGI1 autoantibodies in the sera these patients.

Patients and methods: We examined tumor tissue samples from 24 patients with high-grade gliomas (12 with and 12 without epilepsy) by immunoblot and detected variable amounts of LGI1 in tumor tissues from 9/24 (37%) patients.

Results: LGI1 was detected in 7/12 (58%) patients with epilepsy and in 2/12 (16%) patients without epilepsy (p = 0.0894; Fisher's exact test). Moreover, testing blood sera of five patients for antibodies against LGI1 revealed LGI1 autoantibodies in two patients, both suffering from epilepsy and expressing LGI1 in tumor tissue.

Conclusion: Our findings suggest that there may be a preferential expression of LGI1 in high-grade glioma tumors of patients with epilepsy. We also unveil the presence of serum LGI1 autoantibodies in some patients with high-grade gliomas, where they might play an epileptogenic role.

Keywords: Epilepsy; GB; Glioblastoma; High-grade glioma; LGI1 autoantibodies.

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / blood*
  • Astrocytoma / diagnosis
  • Astrocytoma / genetics
  • Autoantibodies / blood*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / blood*
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Epilepsy, Temporal Lobe / blood*
  • Epilepsy, Temporal Lobe / diagnosis
  • Epilepsy, Temporal Lobe / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / blood*
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics
  • Glioma / blood
  • Glioma / diagnosis
  • Glioma / genetics
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Proteins / genetics
  • Proteins / metabolism*
  • Young Adult

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Proteins