Causal role of peripheral immune cells in epilepsy: A large-scale genetic correlation study

• Published in: International immunopharmacology Vol. 142; no. Pt B; p. 113238
• Main Authors: Zhao, Ting, Cui, Junshuan, Lan, Shengjiao, Chu, Liangzhao, Tian, Shufen, Zhou, Xingwang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-12-2024
• Subjects: Epilepsy; Immune; Linkage disequilibrium score regression; Mendelian randomization; GWAS; BBB; Epilepsy; MFIs; HS; IVW; TBNK; TLE; AEDs; FDR; Linkage disequilibrium score regression; SNPs; CCL2; TBI; AIE; APCs; AC; cDC; MP; JME; AE; ILAE; MR; ASMs; CAE; Immune; IVs; LDSC; Mendelian randomization; JAE; RC; NORSE; LD; GABA; GTCS; NK; TLRs; DC
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.113238

•The Maturation stages of T cell serve as a protective factor for epilepsy and generalized epilepsy.•Myeloid cell is specifically protective for generalized epilepsy.•cDC may have the ability to promote development of generalized epilepsy with tonic-clonic seizures.
While an increasing number of researchers have focused on the correlation between the immune system and epilepsy, the precise causal role of immune cells in epilepsy continues to elude scientific understanding. The aim of the study was to examine the causal relationship between peripheral immune phenotypes and epilepsy.
Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) were utilized to determine the causal relationship between 731 immune cell traits and various types of epilepsy in this study.
LDSC revealed that 80 immunophenotypes showed genetic correlation with epilepsy, including 58 immunophenotypes associated with a single type of epilepsy (72.5 %),14 immunophenotypes associated with two types of epilepsy (17.5 %),7 immunophenotypes with 3 types of epilepsy (8.75 %) and 1 immunophenotype with 5 types of epilepsy (1.25 %). Although none of the types of epilepsy had a statistically significant effect on immunophenotypes, it is noteworthy that the MR revealed the protective effects of five immunophenotypes on epilepsy: CD45RA+CD8br AC (OR:0.86, 95 %CI:0.80–0.93), FSC-A on myeloid DC (OR:0.95, 95 %CI:0.91–0.98）, CM CD8br AC (OR:0.69, 95 %CI:0.59––0.82), CD33 on CD66b++ Myeloid cell (OR:0.88, 95 %CI:0.83–0.93) and CD127 on CD28- CD8br (OR:0.97, 95 %CI:0.95–0.98). Additionally, harmful effects were observed for two immunophenotypes on epilepsy:CD4 Treg %CD4 (OR:1.04, 95 %CI:1.02–1.06) and SSC-A on plasmacytoid DC (OR:1.01, 95 %CI:1.00–1.02).
Our research has demonstrated the causal connections between immune cells and epilepsy, potentially providing valuable insights for future clinical studies.