Deciphering the circulating immunological landscape of thoracic aortic aneurysm: Insights from a two-sample Mendelian randomization study

Background: Thoracic Aortic Aneurysm (TAA) poses significant health risks due to aortic dilation. Recent evidence suggests a pivotal role for the immune-inflammatory response in the mechanism of aortic aneurysm formation. In this study, we aim to investigate the causal relationship between circulating immune cells and TAA. Methods: This study employs a two-sample Mendelian Randomization (MR) approach, utilizing genome-wide association study (GWAS) summary statistics for 731 immune cell types and two TAA data from large-scale studies. Causal effects of both peripheral immune cells on TAA and TAA on peripheral immune cells are explored. To ensure more accurate results, we intersected the findings from two TAA data from large-scale studies, excluding results where the direction of the odds ratio (OR) was inconsistent. Findings: The study identifies specific immune cells associated with TAA. Notably, CD45+ NKT cell (OR: 0.95, 95CI%: 0.90-0.99 in FinnGen study; OR: 0.91, 95CI%: 0.84-0.99 in CHIP + MGI study) and CD45+ HLA-DR + CD8+ T cells (OR: 0.95, 95CI%: 0.90-0.99 in FinnGen study; OR: 0.90, 95CI%: 0.82-0.99 in CHIP + MGI study) demonstrate a protective role against TAA. In addition, CD28+ CD45RA- CD8+ T cells (relative cell counts and absolute cell counts) and HVEM + CM + CD8+ T cells are adversely affected by TAA. Interpretation: The findings indicate that the potential protective influence exerted by specific subsets of peripheral NKT cells and CD8+ T cells in mitigating the development of TAA, while simultaneously highlighting the reciprocal effects of TAA on peripheral Treg cells subsets and T cell subsets. The complex interaction between immune cells and TAA could provide valuable clues for earlier detection and more efficacious treatment strategies for TAA.