{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:45:13Z","timestamp":1792518313788,"version":"4.5.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370443"],"award-info":[{"award-number":["81370443"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health Commission","doi-asserted-by":"publisher","award":["lingjunrencai-02-06"],"award-info":[{"award-number":["lingjunrencai-02-06"]}],"id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Lifelong exposure to elevated low-density lipoprotein cholesterol in familial hypercholesterolaemia (FH) patients not only increases the risk of atherosclerotic cardiovascular disease, but also affects other organs beyond the cardiovascular system. In a large FH cohort, this study investigated the effects of hypercholesterolaemia on the thymic output and explored whether lipid-lowering therapy can reverse these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>According to the Dutch Lipid Clinic Network criteria, 562 heterozygous FH patients (236 treatment-na\u00efve, 326 on lipid-lowering therapy) and 295 age-matched healthy controls (HCs) were enrolled. Thymic output was measured by circulating CD4+ recent thymic emigrants (RTEs) with flow cytometry, and T-cell receptor excision circles in sorted na\u00efve CD4+ and CD8+ T cells. Repertoire diversity and clonal expansion were evaluated by T-cell receptor beta sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with HCs, treatment-na\u00efve FH patients displayed a significantly reduced percentage of CD4+ RTE among na\u00efve CD4+ T cells, particularly in those aged 18\u201330 years or carrying highly pathogenic LDLR variants. T-cell receptor excision circle analysis supported reduced thymic output in both CD4+ and CD8+ na\u00efve T cells. Quantified thymic ageing further showed that FH patients reached the median CD4+ RTE percentage of HCs \u223c6 years earlier (males: 19.12 vs 25.51 years; females: 19.18 vs 25.58 years). Consistent with reduced thymic output, FH patients showed skewing towards high-frequency T-cell receptor beta clones. Statin-treated FH patients, particularly females, showed higher circulating CD4+ RTE levels than statin-na\u00efve FH patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hypercholesterolaemia was associated with reduced thymic output, while statin-treated patients showed partially preserved circulating CD4+ RTE levels, supporting integrated metabolic and immunologic strategies for FH management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehag810","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:28:40Z","timestamp":1792517320000},"source":"Crossref","is-referenced-by-count":0,"title":["Familial hypercholesterolaemia and thymic ageing in a Chinese 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