Controversies regarding thymectomy on immune function_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIN Xiaoting ^1,2,3 , PAN Zuling ^1,2,3 , LIU Peng ^1,2,3 ,  QI Guoyan ^1,2,3

1. Myasthenia Gravis Diagnosis and Treatment Center of Hebei Province, Shijiazhuang People's Hospital, Shijiazhuang, 050000, P. R. China;
2. Hebei Province Key Laboratory of Myasthenia Gravis, Shijiazhuang, 050000, P. R. China;
3. Hebei Province Clinical Medical Research Center for Myasthenia Gravis, Shijiazhuang, 050000, P. R. China;

Corresponding?author：

QI Guoyan, Email: zzjwlsys@163.com

Keywords：

Thymus; thymectomy; immune function effects; myasthenia gravis

DOI：

10.7507/1007-4848.202511040

Video：

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The thymus is a key organ for the development and maturation of T cells, and its resection may have profound effects on the body’s immune function. Postoperative immune alterations may include reduced diversity of the T-cell repertoire, accelerated immune senescence, and dysfunction of regulatory T cells (Tregs). There may also be an increased long-term risk of infections, autoimmune diseases, and tumors. Furthermore, the immunological impact varies significantly among different populations and between partial and total thymectomy. Current research findings remain controversial, limited by factors such as substantial population heterogeneity and short follow-up periods. Future studies should involve multicenter, long-term, large-scale follow-up research. Additionally, individualized surgical and intervention strategies should be developed to improve the long-term prognosis of patients.

1.	Stosio M, Ruszkowski J, Mikosik-Roczyńska A, et al. The significance of neonatal thymectomy for shaping the immune system in children with congenital heart defects. Kardiochir Torakochirurgia Pol, 2017, 14(4): 258-262.
2.	Steinmann GG, Klaus B, Müller-Hermelink HK. The involution of the ageing human thymic epithelium is independent of puberty. a morphometric study. Scand J Immunol, 1985, 22(5): 563-575.
3.	Jamieson BD, Douek DC, Killian S, et al. Generation of functional thymocytes in the human adult. Immunity, 1999, 10(5): 569-575.
4.	Naylor K, Li G, Vallejo AN, et al. The influence of age on T cell generation and TCR diversity. J Immunol, 2005, 174(11): 7446-7452.
5.	Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature, 1998, 396(6712): 690-695.
6.	Kooshesh KA, Foy BH, Sykes DB, et al. Health consequences of thymus removal in adults. N Engl J Med, 2023, 389(5): 406-417.
7.	Asnaghi MA, Barthlott T, Gullotta F, et al. Thymus extracellular matrix-derived scaffolds support graft-resident thymopoiesis and long-term in vitro culture of adult thymic epithelial cells. Adv Funct Mater, 2021, 31(20): 2010747.
8.	Kondo K, Ohigashi I, Takahama Y. Thymus machinery for T-cell selection. Int Immunol, 2019, 31(3): 119-125.
9.	Wang H, Zú?iga-Pflücker JC. Thymic microenvironment: interactions between innate immune cells and developing thymocytes. Front Immunol, 2022, 13: 885280.
10.	Ferreirinha P, Pinheiro RGR, Landry JJM, et al. Identification of fibroblast progenitors in the developing mouse thymus. Development, 2022, 149(10): dev200513.
11.	Muro R, Nitta T. It‘s time to unite: diversity and coordination of thymic stromal cells for T cell selection and organ integrity. Immunol Rev, 2025, 332(1): e70040.
12.	Cavalcanti NV, Palmeira P, Jatene MB, et al. Early thymectomy is associated with long-term impairment of the immune system: a systematic review. Front Immunol, 2021, 12: 774780.
13.	Popperud TH, Gul KA, Brunborg C, et al. Thymectomy in juvenile myasthenia gravis is safe regarding long term immunological effects. Front Neurol, 2021, 12: 596859.
14.	Bains I, Thiébaut R, Yates AJ, et al. Quantifying thymic export: combining models of naive T cell proliferation and TCR excision circle dynamics gives an explicit measure of thymic output. J Immunol, 2009, 183(7): 4329-4336.
15.	Zhang B, Jia Q, Bock C, et al. Glimpse of natural selection of long-lived T-cell clones in healthy life. Proc Natl Acad Sci U S A, 2016, 113(35): 9858-9863.
16.	Bernaldo-de-Quirós E, López-Abente J, Camino M, et al. The presence of a marked imbalance between regulatory T cells and effector T cells reveals that tolerance mechanisms could be compromised in heart transplant children. Transplant Direct, 2021, 7(5): e693.
17.	Herbin O, Bonito AJ, Jeong S, et al. Medullary thymic epithelial cells and CD8α+ dendritic cells coordinately regulate central tolerance but CD8α+ cells are dispensable for thymic regulatory T cell production. J Autoimmun, 2016, 75: 141-149.
18.	Almeida-Santos J, Bergman ML, Cabral IA, et al. Interruption of thymic activity in adult mice improves responses to tumor immunotherapy. J Immunol, 2021, 206(5): 978-986.
19.	Severin ME, Lee PW, Liu Y, et al. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis. Brain, 2016, 139(Pt 6): 1747-1761.
20.	Lee V, Rodriguez DM, Ganci NK, et al. The endogenous repertoire harbors self-reactive CD4+ T cell clones that adopt a follicular helper T cell-like phenotype at steady state. Nat Immunol, 2023, 24(3): 487-500.
21.	Silva SL, Albuquerque A, Amaral AJ, et al. Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy. PLoS One, 2017, 12(7): e0180385.
22.	Merz M, Hu Q, Merz AMA, et al. Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma. Blood Adv, 2023, 7(5): 718-733.
23.	Goggins JA, Kurtz JR, McLachlan JB. Control of persistent Salmonella infection relies on constant thymic output despite increased peripheral antigen-specific T cell immunity. Pathogens, 2020, 9(8): 605.
24.	Rantanen R, Honkila M, K?m? HR, et al. Pneumonia, wheezing and asthma were more common in children after thymectomy due to open-heart surgery. Acta Paediatr, 2024, 113(7): 1685-1693.
25.	Gudmundsdottir J, S?derling J, Berggren H, et al. Long-term clinical effects of early thymectomy: associations with autoimmune diseases, cancer, infections, and atopic diseases. J Allergy Clin Immunol, 2018, 141(6): 2294-2297. e8.
26.	Roosen J, Oosterlinck W, Meyns B. Routine thymectomy in congenital cardiac surgery changes adaptive immunity without clinical relevance. Interact Cardiovasc Thorac Surg, 2015, 20(1): 101-106.
27.	Halnon NJ, Jamieson B, Plunkett M, et al. Thymic function and impaired maintenance of peripheral T cell populations in children with congenital heart disease and surgical thymectomy. Pediatr Res, 2005, 57(1): 42-48.
28.	Schadenberg AW, van den Broek T, Siemelink MA, et al. Differential homeostatic dynamics of human regulatory T-cell subsets following neonatal thymectomy. J Allergy Clin Immunol, 2014, 133(1): 277-280. e6.
29.	Detterbeck FC, Kaminski HJ, Blasberg JD, et al. Does thymectomy in adults have long-term health consequences?. J Thorac Cardiovasc Surg, 2025, 169(3): 787-795. e2.
30.	Bilgic-Eltan S, Amirov R, Babayeva R, et al. Long-term immunological changes after corrective cardiac surgery. Scand J Immunol, 2024, 100(6): e13418.
31.	Kes?l?inen A, Rantanen R, Honkila M, et al. Effects of antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability following paediatric open-heart surgery and thymectomy: a single-centre retrospective cohort study. BMJ Paediatr Open, 2024, 8(1): e002651.
32.	Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med, 2016, 375(6): 511-522.
33.	Chang CC, Lin TM, Chang YS, et al. Thymectomy in patients with myasthenia gravis increases the risk of autoimmune rheumatic diseases: a nationwide cohort study. Rheumatology (Oxford), 2019, 58(1): 135-143.
34.	Filosso PL, Galassi C, Ruffini E, et al. Thymoma and the increased risk of developing extrathymic malignancies: a multicentre study. Eur J Cardiothorac Surg, 2013, 44(2): 219-224.
35.	Masaoka A, Yamakawa Y, Niwa H, et al. Thymectomy and malignancy. Eur J Cardiothorac Surg, 1994, 8(5): 251-253.
36.	Kurobe H, Tominaga T, Sugano M, et al. Complete but not partial thymectomy in early infancy reduces T-cell-mediated immune response: three-year tracing study after pediatric cardiac surgery. J Thorac Cardiovasc Surg, 2013, 145(3): 656-662.
37.	Afifi A, Raja SG, Pennington DJ, et al. For neonates undergoing cardiac surgery does thymectomy as opposed to thymic preservation have any adverse immunological consequences?. Interact Cardiovasc Thorac Surg, 2010, 11(3): 287-291.
38.	Resio BJ, Canavan M, Caturegli G, et al. Mortality risk and cause of death associated with removal of the adult thymus: analysis of the U. S. thymoma population. J Thorac Oncol, 2025, 20(8): 1345-1548.
39.	Dion ML, Sékaly RP, Cheynier R. Estimating thymic function through quantification of T-cell receptor excision circles. Methods Mol Biol, 2007, 380: 197-213.
40.	Middelkamp V, Kek?l?inen E. Measuring thymic output across the human lifespan: a critical challenge in laboratory medicine. Geroscience, 2025, 47(6): 6797-6806.
41.	Wysoczańska B. Kolista czasteczka DNA-TREC jako marker prawid?owej funkcji grasicy [T-cell receptor rearrangement excision circles (TRECs) as a marker of thymic function]. Postepy Hig Med Dosw (Online), 2008, 62: 708-724.
42.	Sandhar B, Vyas V, Harding D, et al. Heterogeneity of thymic output in the elderly and its association with sex and smoking. JCI Insight, 2025, 10(15): e189008.
43.	Hayashi T, Okazaki M, Mitsuhashi T, et al. Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis. Int J Surg, 2025, 111: 101886.
44.	Kim AG, Upah SA, Brandsema JF, et al. Thoracoscopic thymectomy for juvenile myasthenia gravis. Pediatr Surg Int, 2019, 35(5): 603-610.
45.	See KC. Vaccination for the prevention of infection among immunocompromised patients: a concise review of recent systematic reviews. Vaccines (Basel), 2022, 10(5): 800.
46.	Pala F, Notarangelo LD, Lionakis MS. Thymic inborn errors of immunity. J Allergy Clin Immunol, 2025, 155(2): 368-376.
47.	Dong JP, Gao W, Teng GG, et al. Characteristics of Good’s syndrome in China: a systematic review. Chin Med J (Engl), 2017, 130(13): 1604-1609.
48.	Chaudhry MS, Velardi E, Dudakov JA, et al. Thymus: the next (re)generation. Immunol Rev, 2016, 271(1): 56-71.
49.	Duah M, Li L, Shen J, et al. Thymus degeneration and regeneration. Front Immunol, 2021, 12: 706244.
50.	Kinsella S, Dudakov JA. When the damage is done: injury and repair in thymus function. Front Immunol, 2020, 11: 1745.
51.	Moore EM, Maestas DR Jr, Comeau HY, et al. The immune system and its contribution to variability in regenerative medicine. Tissue Eng Part B Rev, 2021, 27(1): 39-47.
52.	Okuda K, Hattori H, Yokota K, et al. Examination on the necessity of pericardial fat tissue resection in extended thymectomy for myasthenia gravis. Gland Surg, 2021, 10(8): 2438-2444.
53.	Li F, Tao Y, Bauer G, et al. Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis. J Thorac Dis, 2019, 11(9): 4039-4048.

1. Stosio M, Ruszkowski J, Mikosik-Roczyńska A, et al. The significance of neonatal thymectomy for shaping the immune system in children with congenital heart defects. Kardiochir Torakochirurgia Pol, 2017, 14(4): 258-262.
2. Steinmann GG, Klaus B, Müller-Hermelink HK. The involution of the ageing human thymic epithelium is independent of puberty. a morphometric study. Scand J Immunol, 1985, 22(5): 563-575.
3. Jamieson BD, Douek DC, Killian S, et al. Generation of functional thymocytes in the human adult. Immunity, 1999, 10(5): 569-575.
4. Naylor K, Li G, Vallejo AN, et al. The influence of age on T cell generation and TCR diversity. J Immunol, 2005, 174(11): 7446-7452.
5. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature, 1998, 396(6712): 690-695.
6. Kooshesh KA, Foy BH, Sykes DB, et al. Health consequences of thymus removal in adults. N Engl J Med, 2023, 389(5): 406-417.
7. Asnaghi MA, Barthlott T, Gullotta F, et al. Thymus extracellular matrix-derived scaffolds support graft-resident thymopoiesis and long-term in vitro culture of adult thymic epithelial cells. Adv Funct Mater, 2021, 31(20): 2010747.
8. Kondo K, Ohigashi I, Takahama Y. Thymus machinery for T-cell selection. Int Immunol, 2019, 31(3): 119-125.
9. Wang H, Zú?iga-Pflücker JC. Thymic microenvironment: interactions between innate immune cells and developing thymocytes. Front Immunol, 2022, 13: 885280.
10. Ferreirinha P, Pinheiro RGR, Landry JJM, et al. Identification of fibroblast progenitors in the developing mouse thymus. Development, 2022, 149(10): dev200513.
11. Muro R, Nitta T. It‘s time to unite: diversity and coordination of thymic stromal cells for T cell selection and organ integrity. Immunol Rev, 2025, 332(1): e70040.
12. Cavalcanti NV, Palmeira P, Jatene MB, et al. Early thymectomy is associated with long-term impairment of the immune system: a systematic review. Front Immunol, 2021, 12: 774780.
13. Popperud TH, Gul KA, Brunborg C, et al. Thymectomy in juvenile myasthenia gravis is safe regarding long term immunological effects. Front Neurol, 2021, 12: 596859.
14. Bains I, Thiébaut R, Yates AJ, et al. Quantifying thymic export: combining models of naive T cell proliferation and TCR excision circle dynamics gives an explicit measure of thymic output. J Immunol, 2009, 183(7): 4329-4336.
15. Zhang B, Jia Q, Bock C, et al. Glimpse of natural selection of long-lived T-cell clones in healthy life. Proc Natl Acad Sci U S A, 2016, 113(35): 9858-9863.
16. Bernaldo-de-Quirós E, López-Abente J, Camino M, et al. The presence of a marked imbalance between regulatory T cells and effector T cells reveals that tolerance mechanisms could be compromised in heart transplant children. Transplant Direct, 2021, 7(5): e693.
17. Herbin O, Bonito AJ, Jeong S, et al. Medullary thymic epithelial cells and CD8α+ dendritic cells coordinately regulate central tolerance but CD8α+ cells are dispensable for thymic regulatory T cell production. J Autoimmun, 2016, 75: 141-149.
18. Almeida-Santos J, Bergman ML, Cabral IA, et al. Interruption of thymic activity in adult mice improves responses to tumor immunotherapy. J Immunol, 2021, 206(5): 978-986.
19. Severin ME, Lee PW, Liu Y, et al. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis. Brain, 2016, 139(Pt 6): 1747-1761.
20. Lee V, Rodriguez DM, Ganci NK, et al. The endogenous repertoire harbors self-reactive CD4+ T cell clones that adopt a follicular helper T cell-like phenotype at steady state. Nat Immunol, 2023, 24(3): 487-500.
21. Silva SL, Albuquerque A, Amaral AJ, et al. Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy. PLoS One, 2017, 12(7): e0180385.
22. Merz M, Hu Q, Merz AMA, et al. Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma. Blood Adv, 2023, 7(5): 718-733.
23. Goggins JA, Kurtz JR, McLachlan JB. Control of persistent Salmonella infection relies on constant thymic output despite increased peripheral antigen-specific T cell immunity. Pathogens, 2020, 9(8): 605.
24. Rantanen R, Honkila M, K?m? HR, et al. Pneumonia, wheezing and asthma were more common in children after thymectomy due to open-heart surgery. Acta Paediatr, 2024, 113(7): 1685-1693.
25. Gudmundsdottir J, S?derling J, Berggren H, et al. Long-term clinical effects of early thymectomy: associations with autoimmune diseases, cancer, infections, and atopic diseases. J Allergy Clin Immunol, 2018, 141(6): 2294-2297. e8.
26. Roosen J, Oosterlinck W, Meyns B. Routine thymectomy in congenital cardiac surgery changes adaptive immunity without clinical relevance. Interact Cardiovasc Thorac Surg, 2015, 20(1): 101-106.
27. Halnon NJ, Jamieson B, Plunkett M, et al. Thymic function and impaired maintenance of peripheral T cell populations in children with congenital heart disease and surgical thymectomy. Pediatr Res, 2005, 57(1): 42-48.
28. Schadenberg AW, van den Broek T, Siemelink MA, et al. Differential homeostatic dynamics of human regulatory T-cell subsets following neonatal thymectomy. J Allergy Clin Immunol, 2014, 133(1): 277-280. e6.
29. Detterbeck FC, Kaminski HJ, Blasberg JD, et al. Does thymectomy in adults have long-term health consequences?. J Thorac Cardiovasc Surg, 2025, 169(3): 787-795. e2.
30. Bilgic-Eltan S, Amirov R, Babayeva R, et al. Long-term immunological changes after corrective cardiac surgery. Scand J Immunol, 2024, 100(6): e13418.
31. Kes?l?inen A, Rantanen R, Honkila M, et al. Effects of antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability following paediatric open-heart surgery and thymectomy: a single-centre retrospective cohort study. BMJ Paediatr Open, 2024, 8(1): e002651.
32. Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med, 2016, 375(6): 511-522.
33. Chang CC, Lin TM, Chang YS, et al. Thymectomy in patients with myasthenia gravis increases the risk of autoimmune rheumatic diseases: a nationwide cohort study. Rheumatology (Oxford), 2019, 58(1): 135-143.
34. Filosso PL, Galassi C, Ruffini E, et al. Thymoma and the increased risk of developing extrathymic malignancies: a multicentre study. Eur J Cardiothorac Surg, 2013, 44(2): 219-224.
35. Masaoka A, Yamakawa Y, Niwa H, et al. Thymectomy and malignancy. Eur J Cardiothorac Surg, 1994, 8(5): 251-253.
36. Kurobe H, Tominaga T, Sugano M, et al. Complete but not partial thymectomy in early infancy reduces T-cell-mediated immune response: three-year tracing study after pediatric cardiac surgery. J Thorac Cardiovasc Surg, 2013, 145(3): 656-662.
37. Afifi A, Raja SG, Pennington DJ, et al. For neonates undergoing cardiac surgery does thymectomy as opposed to thymic preservation have any adverse immunological consequences?. Interact Cardiovasc Thorac Surg, 2010, 11(3): 287-291.
38. Resio BJ, Canavan M, Caturegli G, et al. Mortality risk and cause of death associated with removal of the adult thymus: analysis of the U. S. thymoma population. J Thorac Oncol, 2025, 20(8): 1345-1548.
39. Dion ML, Sékaly RP, Cheynier R. Estimating thymic function through quantification of T-cell receptor excision circles. Methods Mol Biol, 2007, 380: 197-213.
40. Middelkamp V, Kek?l?inen E. Measuring thymic output across the human lifespan: a critical challenge in laboratory medicine. Geroscience, 2025, 47(6): 6797-6806.
41. Wysoczańska B. Kolista czasteczka DNA-TREC jako marker prawid?owej funkcji grasicy [T-cell receptor rearrangement excision circles (TRECs) as a marker of thymic function]. Postepy Hig Med Dosw (Online), 2008, 62: 708-724.
42. Sandhar B, Vyas V, Harding D, et al. Heterogeneity of thymic output in the elderly and its association with sex and smoking. JCI Insight, 2025, 10(15): e189008.
43. Hayashi T, Okazaki M, Mitsuhashi T, et al. Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis. Int J Surg, 2025, 111: 101886.
44. Kim AG, Upah SA, Brandsema JF, et al. Thoracoscopic thymectomy for juvenile myasthenia gravis. Pediatr Surg Int, 2019, 35(5): 603-610.
45. See KC. Vaccination for the prevention of infection among immunocompromised patients: a concise review of recent systematic reviews. Vaccines (Basel), 2022, 10(5): 800.
46. Pala F, Notarangelo LD, Lionakis MS. Thymic inborn errors of immunity. J Allergy Clin Immunol, 2025, 155(2): 368-376.
47. Dong JP, Gao W, Teng GG, et al. Characteristics of Good’s syndrome in China: a systematic review. Chin Med J (Engl), 2017, 130(13): 1604-1609.
48. Chaudhry MS, Velardi E, Dudakov JA, et al. Thymus: the next (re)generation. Immunol Rev, 2016, 271(1): 56-71.
49. Duah M, Li L, Shen J, et al. Thymus degeneration and regeneration. Front Immunol, 2021, 12: 706244.
50. Kinsella S, Dudakov JA. When the damage is done: injury and repair in thymus function. Front Immunol, 2020, 11: 1745.
51. Moore EM, Maestas DR Jr, Comeau HY, et al. The immune system and its contribution to variability in regenerative medicine. Tissue Eng Part B Rev, 2021, 27(1): 39-47.
52. Okuda K, Hattori H, Yokota K, et al. Examination on the necessity of pericardial fat tissue resection in extended thymectomy for myasthenia gravis. Gland Surg, 2021, 10(8): 2438-2444.
53. Li F, Tao Y, Bauer G, et al. Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis. J Thorac Dis, 2019, 11(9): 4039-4048.

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