Deciphering Abdominal Aortic Diseases Through T‐Cell Clonal Repertoire of Perivascular Adipose Tissue

Abstract

Background Recent studies suggest that immune‐mediated inflammation of perivascular adipose tissue of abdominal aortic aneurysms (AAAs) contributes to disease development and progression. Whether the perivascular adipose tissue of AAA is characterized by a specific adaptive immune signature remains unknown. Methods and Results To investigate this hypothesis, we sequenced the T‐cell receptor β‐chain in the perivascular adipose tissue of patients with AAA and compared it with patients with aortic occlusive disease, who share the former anatomical site of the lesion and risk factors but differ in pathogenic mechanisms. Our results demonstrate that patients with AAA have a lower repertoire diversity than those with aortic occlusive disease and significant differences in variable/joining gene segment usage. Furthermore, we identified a set of 7 public T‐cell receptor β‐chain clonotypes that distinguished AAA and aortic occlusive disease with very high accuracy. We also found that the T‐cell receptor β‐chain repertoire differentially characterizes small and large AAAs (aortic diameter<55 mm and ≥55 mm, respectively). Conclusions This work supports the hypothesis that T cell–mediated immunity is fundamental in AAA pathogenesis and opens up new clinical perspectives.

Keywords

• abdominal aortic aneurysm
• aortic diseases
• atherosclerosis
• deep sequencing
• T‐cell clonal repertoire