Abstracts

T Cell Receptor Repertoire Analysis in Intractable Epilepsy: Correlation with Seizure Frequency and Brain Atrophy

Abstract number : 1.571
Submission category : 2. Translational Research / 2C. Biomarkers
Year : 2024
Submission ID : 1582
Source : www.aesnet.org
Presentation date : 12/7/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: Yong-Won Shin, MD, PhD – Seoul National University Hospital

Sang Bin Hong, MD, PhD – Seoul National University Hospital
Jangsup Moon, MD, PhD – Seoul National University Hospital
Soon-Tae Lee, MD, PhD – Seoul National University Hospital
Kyung-Il Park, MD, PhD – Seoul National University Hospital
Kon Chu, MD, PhD – Seoul National University Hospital
Sang Kun Lee, MD, PhD – Seoul National University Hospital

Rationale:

A proinflammatory environment, characterized by the infiltration of both innate and adaptive immune cells in epileptic tissue, along with altered systemic immune cell and cytokine profiles, has been documented in epilepsy. T cell receptors (TCRs), located on the surface of T cells, recognize peptide antigens bound to major histocompatibility complexes, playing a critical role in the adaptive immune response. Previous studies have shown changes in TCR repertoire in various autoimmune diseases, including neurological disorders such as multiple sclerosis and Rasmussen encephalitis. In this study, we investigated whether the TCR repertoire in circulating T cells reflects epilepsy associated with inflammatory activity.



Methods: We analyzed the TCR beta-chain repertoires of patients with intractable epilepsy, autoimmune encephalitis, and control subjects using peripheral blood mononuclear cells. Demographic and clinical characteristics of the patients were collected, and volumetric analysis of magnetic resonance imaging (MRI) was performed to assess brain structure.

Results:

A total of 36 subjects were analyzed in this study. Patients with intractable epilepsy (n=16) exhibited increased TCR clonality compared to the control population (n=7), though to a lesser degree than patients with autoimmune encephalitis (n=13) (Kruskal-Wallis p = 0.001). Seizure frequency in the epilepsy patients showed a significant correlation with TCR repertoire clonality (R = 0.53, p=0.043). Additionally, the normalized percentile of the asymmetric index of the temporal lobe demonstrated a strong correlation with TCR repertoire clonality (R = 0.68, p = 0.0081).



Conclusions:

TOur findings indicate that clonally expanded T cells are more prevalent in patients with intractable epilepsy compared to the control population. The degree of TCR clonality correlates with seizure frequency and the extent of brain atrophy, suggesting that TCR repertoire analysis could serve as a marker for epilepsy severity. This study provides evidence of an ongoing adaptive immune process in epilepsy, implying that epileptic activity may be quantifiable through circulating TCR repertoire analysis. Further research is warranted to explore the clinical implications of these findings.



Funding: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (NRF-2020R1C1C1014982).

Translational Research