Massachusetts General Hospital Boston, Massachusetts, United States
Disclosure(s):
Kameron Allen Kooshesh, M.D.: No financial relationships to disclose
Purpose: The function of the thymus in adult humans is unclear, however routine removal is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health. Methods: We compared 1146 adult Mass General Brigham patients who had undergone thymectomy with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T cell production, T cell receptor diversity, and blood plasma cytokine levels were examined in 22 thymectomy and 19 control patients (mean follow-up 14.2 post-operative years). Results: At 5 years after surgery, patients who had undergone thymectomy had higher all-cause mortality than controls (RR [95% CI]: 2.4 [1.3-4.3]) as well as a higher risk of cancer (RR 2.2 [1.1-4.4]) and a higher risk of autoimmune disease (RR 1.5 [1.02-2.2]). The risks of mortality and malignancy remained elevated across 20 post-operative years as evident from Kaplan-Meier analysis (HR 1.5 [1.3-1.7] and HR 1.6 [1.4-1.8] for mortality and malignancy, respectively). In an analysis in which data were adjusted for age, year, and U.S. state, all-cause mortality and mortality due to malignancy were higher among patients who had undergone thymectomy than among the general U.S. population (All-cause mortality: 9.0% [86/951] vs. 5.2% [REFS 1,2]; mortality due to malignancy: 2.3% [22/951] vs. 1.5% [REFS 1,2]). This was accompanied by decreased de novo production of CD4+ and CD8+ lymphocytes than controls (CD4+ signal joint T cell receptor excision circle [sjTREC] counts: 1451 vs. 526, P = 0.009; CD8+ sjTREC count: 1466 vs. 447, P < 0.001) and a decrease in CD4+ and CD8+ T cell receptor repertoire diversity in thymectomy patients (P = 0.02 and P = 0.007, respectively) with higher levels of pro-inflammatory cytokines in the blood. Conclusion: The thymus contributes to new T cell production in adulthood and remains important for adult health, as it has a role in the prevention of mortality, malignancy, and autoimmunity. The adverse consequences of thymic loss should be considered when contemplating thymectomy.
Identify the source of the funding for this research project: Supported by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund, the Gerald and Darlene Jordan Professorship of Medicine, and a grant (U19AI149676, to Dr. Scadden) from the National Institutes of Health. Dr. Kooshesh received support from the American Society of Hematology. Dr. Gustafsson received support from the Swedish Research Council and the John S. Macdougall Jr. and Olive R. Macdougall Fund.
