Deciphering abdominal aortic diseases through T-cell clonal repertoire of perivascular adipose tissue

Abstract

Recent studies suggested that immune-mediated inflammation of perivascular adipose tissue (PVAT) of abdominal aortic aneurysms (AAA) contributes to disease development and progression. Whether the PVAT of AAA is characterized by a specific adaptive immune signature remains unknown. To investigate this hypothesis, we sequenced the T-cell receptor {beta}-chain (TCR{beta}) in the PVAT of AAA patients and compared with patients with aortic occlusive disease (AOD), who share with the former anatomical site of the lesion, risk factors but differ in pathogenic mechanisms. Our results demonstrate that AAA patients have a lower repertoire diversity than those with AOD and significant differences in V/J gene segment usage. Furthermore, we identified a set of 7 public TCR{beta} clonotypes that distinguished AAA and AOD with very high accuracy. We also found that the TCR{beta} repertoire differentially characterizes small and large AAA (aortic diameter <55 mm and [≥]55 mm, respectively). This work supports the hypothesis that T-cell-mediated immunity is fundamental in AAA pathogenesis and opens up new clinical perspectives. SummaryDifferent immune mechanisms may play a key role in the pathogenesis of distal aortic aneurysm and aortoiliac occlusive disease. The TCR{beta} repertoire of perivascular adipose tissue differs between the two pathologic conditions, suggesting the involvement of specific antigen-specific immune responses.