Effect of LGI1 antibody-positive IgG on hippocampal neuron survival: A preliminary study


Ayşit-Altuncu N., Ulusoy C., ÖZTÜRK G., TÜZÜN E.

NeuroReport, vol.29, no.11, pp.932-938, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 29 Issue: 11
  • Publication Date: 2018
  • Doi Number: 10.1097/wnr.0000000000001055
  • Journal Name: NeuroReport
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.932-938
  • Keywords: antibody, apoptosis, autoimmunity, calcium influx, leucine-rich glioma-inactivated 1
  • Istanbul Medipol University Affiliated: Yes

Abstract

Anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis is one of the most frequently encountered forms of autoimmune encephalitis. Many patients with anti-LGI1 encephalitis develop permanent hippocampal neuron loss and chronic neuropsychiatric symptoms, suggesting that LGI antibodies (Ab) might have a neurotoxic action. To investigate this hypothesis, purified serum IgG of three patients with anti-LGI1 encephalitis and six healthy controls were incubated with cultured primary hippocampal neurons obtained from newborn mice. Nontreated cells were used as controls. The viability of IgG-Treated neurons was evaluated by propidium iodide staining. Apoptotic mechanisms were assessed by JC-1 assay and mRNA expression level measurement of apoptosis-related genes using real-Time PCR. The effect of IgG treatment on calcium influx was analyzed by fluo-4 calcium imaging. LGI1-Ab+ IgG increased the number of propidium iodide positive neurons, reduced mitochondrial membrane potentials, upregulated caspase-3 and Bax mRNA expression levels and downregulated Bcl-2 mRNA expression levels of neurons. LGI1-Ab+ IgG-Treated neurons showed lower calcium staining than healthy controls IgG-Treated and non-IgG-Treated neurons. Our results indicate a neurotoxic role of LGI1-Ab. This neurotoxicity is likely mediated through induction of apoptosis and reduction of calcium currents.