关键词: T‐cell clonal repertoire abdominal aortic aneurysm aortic diseases atherosclerosis deep sequencing

Mesh : Humans Aortic Aneurysm, Abdominal / immunology genetics pathology Male Aged Female T-Lymphocytes / immunology Adipose Tissue / pathology immunology Receptors, Antigen, T-Cell, alpha-beta / genetics immunology Middle Aged Aorta, Abdominal / pathology immunology

来  源:   DOI:10.1161/JAHA.123.034096

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.
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.
摘要:
背景:最近的研究表明,免疫介导的腹主动脉瘤(AAAs)血管周围脂肪组织炎症有助于疾病的发展和进展。AAA的血管周围脂肪组织是否以特定的适应性免疫特征为特征仍然未知。
结果:为了研究这一假设,我们对AAA患者血管周围脂肪组织中的T细胞受体β链进行了测序,并将其与主动脉闭塞性疾病患者进行了比较,他们共享病变的前解剖部位和危险因素,但致病机制不同。我们的结果表明,与主动脉闭塞性疾病患者相比,AAA患者的组库多样性较低,并且可变/连接基因片段的使用存在显着差异。此外,我们鉴定了一组7种公共T细胞受体β链克隆型,这些克隆型能够非常准确地区分AAA和主动脉闭塞性疾病.我们还发现,T细胞受体β链库具有小的和大的AAAs(主动脉直径<55mm和≥55mm,分别)。
结论:这项工作支持T细胞介导的免疫是AAA发病机制的基础的假设,并开辟了新的临床观点。
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