From the Centers for Regenerative Medicine (K.A.K., D.B.S., K.G., D.T.S.) and Systems Biology (B.H.F.), Massachusetts General Hospital, the Harvard Stem Cell Institute (K.A.K., K.G., D.T.S.), the Department of Stem Cell and Regenerative Biology, Harvard University (K.A.K., K.G., D.T.S.), and Harvard Medical School (K.A.K., B.H.F., D.B.S., K.G., D.T.S.) - all in Boston.
N Engl J Med. 2023 Aug 3;389(5):406-417. doi: 10.1056/NEJMoa2302892.
The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health.
We evaluated the risk of death, cancer, and autoimmune disease among adult patients who had undergone thymectomy as compared with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T-cell production and plasma cytokine levels were also compared in a subgroup of patients.
After exclusions, 1420 patients who had undergone thymectomy and 6021 controls were included in the study; 1146 of the patients who had undergone thymectomy had a matched control and were included in the primary cohort. At 5 years after surgery, all-cause mortality was higher in the thymectomy group than in the control group (8.1% vs. 2.8%; relative risk, 2.9; 95% confidence interval [CI], 1.7 to 4.8), as was the risk of cancer (7.4% vs. 3.7%; relative risk, 2.0; 95% CI, 1.3 to 3.2). Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2). In an analysis involving all patients with more than 5 years of follow-up (with or without a matched control), all-cause mortality was higher in the thymectomy group than in the general U.S. population (9.0% vs. 5.2%), as was mortality due to cancer (2.3% vs. 1.5%). In the subgroup of patients in whom T-cell production and plasma cytokine levels were measured (22 in the thymectomy group and 19 in the control group; mean follow-up, 14.2 postoperative years), those who had undergone thymectomy had less new production of CD4+ and CD8+ lymphocytes than controls (mean CD4+ signal joint T-cell receptor excision circle [sjTREC] count, 1451 vs. 526 per microgram of DNA [P = 0.009]; mean CD8+ sjTREC count, 1466 vs. 447 per microgram of DNA [P<0.001]) and higher levels of proinflammatory cytokines in the blood.
In this study, all-cause mortality and the risk of cancer were higher among patients who had undergone thymectomy than among controls. Thymectomy also appeared be associated with an increased risk of autoimmune disease when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis. (Funded by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund and others.).
人体成年后的胸腺功能尚不清楚,在各种外科手术中常常规切除胸腺。我们假设成年胸腺是维持免疫功能和整体健康所必需的。
我们评估了接受胸腺切除术的成年患者与接受类似心胸外科手术但未切除胸腺的匹配对照组相比的死亡、癌症和自身免疫性疾病风险。还比较了一组患者的 T 细胞产生和血浆细胞因子水平。
排除后,共有 1420 名接受胸腺切除术的患者和 6021 名对照组患者纳入研究;其中 1146 名接受胸腺切除术的患者有匹配的对照组并纳入主要队列。手术后 5 年,胸腺切除术组的全因死亡率高于对照组(8.1% vs. 2.8%;相对风险,2.9;95%置信区间[CI],1.7 至 4.8),癌症风险也更高(7.4% vs. 3.7%;相对风险,2.0;95%CI,1.3 至 3.2)。尽管在总体主要队列中,两组间自身免疫性疾病的风险差异不大(相对风险,1.1;95%CI,0.8 至 1.4),但当排除术前感染、癌症或自身免疫性疾病的患者进行分析时,差异明显(12.3% vs. 7.9%;相对风险,1.5;95%CI,1.02 至 2.2)。在一项涉及所有随访时间超过 5 年的患者的分析中(无论是否有匹配的对照组),胸腺切除术组的全因死亡率高于美国一般人群(9.0% vs. 5.2%),癌症死亡率也高于美国一般人群(2.3% vs. 1.5%)。在测量 T 细胞产生和血浆细胞因子水平的患者亚组中(胸腺切除术组 22 例,对照组 19 例;平均随访 14.2 年),与对照组相比,接受胸腺切除术的患者新产生的 CD4+和 CD8+淋巴细胞较少(平均 CD4+信号连接 T 细胞受体切除环[sjTREC]计数,1451 与 526 微克 DNA[P=0.009];平均 CD8+ sjTREC 计数,1466 与 447 微克 DNA[P<0.001]),血液中促炎细胞因子水平更高。
在这项研究中,与对照组相比,接受胸腺切除术的患者全因死亡率和癌症风险更高。当排除术前感染、癌症或自身免疫性疾病的患者时,胸腺切除术似乎也与自身免疫性疾病风险增加相关。(由 Tracey 和 Craig A. Huff 哈佛干细胞研究所研究支持基金等资助)。