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Thymoma and autoimmunity

Cellular & Molecular Immunology volume 8, pages 199–202 (2011)Cite this article

Abstract

The thymus is a central lymphatic organ that is responsible for many immunological functions, including the production of mature, functional T cells and the induction of self-tolerance. Benign or malignant tumors may originate from the thymus gland, with thymoma being the most common and accounting for 50% of anterior mediastinal tumors. Malignancies linked to thymoma include the loss of self-tolerance and the presence of autoimmunity. In this review, we compiled the current scientific evidence detailing the various interactions between thymoma and autoimmune diseases, including myasthenia gravis, systemic lupus erythematosus, inappropriate antidiuretic hormone secretion, pure red cell aplasia, pernicious anemia, pemphigus and autoimmune thyroid diseases. In recent years, several mechanisms have been proposed to explain these interactions. Most are based on the assumption that the ‘sick’ thymus, like the ‘normal’ thymus, can generate mature T cells; however, the T cells generated by the sick thymus are impaired and thus may exert cellular autoreactivity. Here, we present several theories that may shed light on the loss of self-tolerance associated with this epithelial tumor of the thymus.

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References

  1. Thomas CR, Wright CD, Loehrer PJ . Thymoma: state of the art. J Clin Oncol 1999; 17: 2280–2289.

    Article  CAS  PubMed  Google Scholar 

  2. Hoffacker V, Schultz A, Tiesinga JJ, Gold R, Schalke B, Nix W et al. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 2000; 96: 3872–3879.

    CAS  PubMed  Google Scholar 

  3. Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004; 77: 1183–1188.

    Article  PubMed  Google Scholar 

  4. Kondo K . Optimal therapy for thymoma. J Med Invest 2008; 55: 17–28.

    Article  PubMed  Google Scholar 

  5. Lucchi M, Basolo F, Ribechini A, Ambrogi MC, Bencivelli S, Fontanini G et al. Thymomas: clinical-pathological correlations. J Cardiovasc Surg (Torino) 2006; 47: 89–93.

    CAS  Google Scholar 

  6. Grob D, Brunner N, Namba T, Pagala M . Lifetime course of myasthenia gravis. Muscle Nerve 2008; 37: 141–149.

    Article  PubMed  Google Scholar 

  7. Gomez AM, van den Broeck J, Vrolix K, Janssen SP, Lemmens MA, van der Esch E et al. Antibody effector mechanisms in myasthenia gravis—pathogenesis at the neuromuscular junction. Autoimmunity 2010; 43: 353–370.

    Article  CAS  PubMed  Google Scholar 

  8. Soltys J, Gong B, Kaminski HJ, Zhou Y, Kusner LL . Extraocular muscle susceptibility to myasthenia gravis: unique immunological environment? Ann NY Acad Sci 2008; 1132: 220–224.

    Article  CAS  PubMed  Google Scholar 

  9. Okumura M, Fujii Y, Shiono H, Inoue M, Minami M, Utsumi T et al. Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis. Gen Thorac Cardiovasc Surg 2008; 56: 143–150.

    Article  PubMed  Google Scholar 

  10. Mygland A, Vincent A, Newsom-Davis J, Kaminski H, Zorzato F, Agius M et al. Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia. Arch Neurol 2000; 57: 527–531.

    Article  CAS  PubMed  Google Scholar 

  11. Ghosh JB, Roy M, Peters T . Thymoma associated with myasthenia gravis in infancy. Indian J Pediatr 2009; 76: 1057–1058.

    Article  CAS  PubMed  Google Scholar 

  12. Chen X, Fang L, Song S, Guo TB, Liu A, Zhang JZ . Thymic regulation of autoimmune disease by accelerated differentiation of Foxp3+ regulatory T cells through IL-7 signaling pathway. J Immunol 2009; 183: 6135–6144.

    Article  CAS  PubMed  Google Scholar 

  13. Shere Y, Bar-Dayan Y, Shoenfeld Y . Tymoma thymic hyperplasia, thymectomy and autoimmune diseases. Int J Oncol 1997; 10: 939–943.

    Google Scholar 

  14. Boonen A, Rennenberg R, van der Linden S . Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. A case report and review of the literature. Rheumatology (Oxford) 2000; 39: 1044–1046.

    Article  CAS  Google Scholar 

  15. Souadjian JV, Enriquez P, Silverstein MN, Pepin JM . The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med 1974; 134: 374–379.

    Article  CAS  PubMed  Google Scholar 

  16. Rosman A, Atsumi T, Khamashta MA, Ames PR, Hughes GR . Development of systemic lupus erythematosus after chemotherapy and radiotherapy for malignant thymoma. Br J Rheumatol 1995; 34: 1175–1176.

    Article  CAS  PubMed  Google Scholar 

  17. Zandman-Goddard G, Lorber M, Shoenfeld Y . Systemic lupus erythematosus and thymoma—a double-edged sword. Int Arch Allergy Immunol 1995; 108: 99–102.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang L, Dong J, Leng XM, Zeng XF . A meta-analysis of thymoma-associated systemic lupus erythematosus from 1975–2008 worldwide. Zhonghua Nei Ke Za Zhi 2009; 48: 643–646. Chinese.

    PubMed  Google Scholar 

  19. Park MJ, Kim YA, Lee SS, Kim BC, Kim MK, Cho KH . Appearance of systemic lupus erythematosus in patients with myasthenia gravis following thymectomy: two case reports. J Korean Med Sci 2004; 19: 134–136.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mevorach D, Perrot S, Buchanan NM, Khamashta M, Laoussadi S, Hughes GR et al. Appearance of systemic lupus erythematosus after thymectomy: four case reports and review of the literature. Lupus 1995; 4: 33–37.

    Article  CAS  PubMed  Google Scholar 

  21. Bozzolo E, Bellone M, Quaroni N, Voci C, Sabbadini MG . Thymoma associated with systemic lupus erythematosus and immunologic abnormalities. Lupus 2000; 9: 151–154.

    Article  CAS  PubMed  Google Scholar 

  22. Gaman A, Gaman G, Bold A . Acquired aplastic anemia: correlation between etiology, pathophysiology, bone marrow histology and prognosis factors. Rom J Morphol Embryol 2009; 50: 669–674.

    PubMed  Google Scholar 

  23. Thompson CA, Steensma DP . Pure red cell aplasia associated with thymoma: clinical insights from a 50-year single-institution experience. Br J Haematol 2006; 135: 405–407.

    Article  PubMed  Google Scholar 

  24. Galesic K, Krizanac S, Vrkljan M, Ljubanovic D . Syndrome of inappropriate secretion of antidiuretic hormone due to malignant thymoma. Nephron 2002; 91: 752–754.

    Article  CAS  PubMed  Google Scholar 

  25. Donadio AC, Dragnev KH, Schwartz GK . Thymoma associated with syndrome of inappropriate antidiuretic hormone secretion and myasthenia gravis. South Med J 1998; 91: 278–279.

    Article  CAS  PubMed  Google Scholar 

  26. Mutasim DF . Autoimmune bullous dermatoses in the elderly: an update on pathophysiology, diagnosis and management. Drugs Aging 2010; 27: 1–19.

    Article  PubMed  Google Scholar 

  27. Souteyrand P, Berthier-Boachon M, Thivolet J . Pemphigus and thymoma: review and etiopathogenesis (author's transl). Ann Dermatol Venereol 1981; 108: 457–467. French.

    CAS  PubMed  Google Scholar 

  28. Barbetakis N, Samanidis G, Paliouras D, Boukovinas I, Asteriou C, Stergiou E et al. Paraneoplastic pemphigus regression after thymoma resection. World J Surg Oncol 2008; 6: 83.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Davila DG, Ryan DH . Thymoma, hypogammaglobulinemia, and pernicious anemia. South Med J 1986; 79: 904–906.

    Article  CAS  PubMed  Google Scholar 

  30. Elliott GB, Hill M, Howard DL . Whipple's disease associated with benign thymoma. Can Med Assoc J 1961; 85: 1340–1344.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. de Keyzer K, Peeters P, Verhelst C, Dendooven A, Vonck A, Vanholder R . Autoimmune haemolytic anaemia associated with a thymoma: case report and review of the literature. Acta Clin Belg 2009; 64: 447–451.

    Article  CAS  PubMed  Google Scholar 

  32. Hammoud K, Kandimala G, Warnack W, Vernino S . Multifocal paraneoplastic cortical encephalitis associated with myasthenia gravis and thymoma. Arch Neurol 2009; 66: 1407–1409.

    Article  PubMed  Google Scholar 

  33. Arbib F, Bejui F, Bouvier R, Ninet J, Guerin JC . Thymoma and primary Gougerot–Sjogren syndrome progressing to severe bronchiolitis. Rev Mal Respir 1993; 10: 465–467. French.

    CAS  PubMed  Google Scholar 

  34. Yoshida H, Matsuda S, Abe R, Kimura H, Shichishima T, Tanaka T et al. Sjogren's syndrome associated with a benign thymic tumor: report of a case with wide spectrum of clinical feature (author's transl). Nippon Ketsueki Gakkai Zasshi 1980; 43: 834–841. Japanese.

    CAS  PubMed  Google Scholar 

  35. Lee BW, Ihm SH, Shin HS, Yoo HJ . Malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH. Intern Med 2008; 47: 1009–1012.

    Article  PubMed  Google Scholar 

  36. Kabelitz D, Schreiber S . Autoimmunity. Physiological control mechanisms and pathways to autoimmune disease. Internist (Berl) 2009; 50 : 267–275. German.

    Article  CAS  Google Scholar 

  37. Wang L . Adaptive Treg generation by DCs and their functional analysis. Methods Mol Biol 2010; 595: 403–412.

    Article  CAS  PubMed  Google Scholar 

  38. Wing K, Sakaguchi S . Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 2010; 11: 7–13.

    Article  CAS  PubMed  Google Scholar 

  39. Chilosi M, Iannucci A, Menestrina F, Lestani M, Scarpa A, Bonetti F et al. Immunohistochemical evidence of active thymocyte proliferation in thymoma. Its possible role in the pathogenesis of autoimmune diseases. Am J Pathol 1987; 128: 464–470.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Shoenfeld Y, Lorber M, Yucel T, Yazici H . Primary antiphospholipid syndrome emerging following thymectomy for myasthenia gravis: additional evidence for the kaleidoscope of autoimmunity. Lupus 1997; 6: 474–476.

    Article  CAS  PubMed  Google Scholar 

  41. Vincent A, Willcox N . The role of T-cells in the initiation of autoantibody responses in thymoma patients. Pathol Res Pract 1999; 195: 535–540.

    Article  CAS  PubMed  Google Scholar 

  42. Tokunaga T, Hayashi A, Kadota Y, Shiono H, Inoue M, Sawabata N et al. Regulation of Th-POK and Runx3 in T cell development in human thymoma. Autoimmunity 2009; 42: 653–660.

    Article  CAS  PubMed  Google Scholar 

  43. Kyewski BA . Thymic dendritic cells present blood-borne antigens to medullary thymocytes in vivo: a possible role in the generation of the T-cell repertoire. Haematol Blood Transfus 1985; 29: 486–491.

    CAS  PubMed  Google Scholar 

  44. Theofilopoulos AN, Dummer W, Kono DH . T cell homeostasis and systemic autoimmunity. J Clin Invest 2001; 108: 335–340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Machens A, Loliger C, Pichlmeier U, Emskotter T, Busch C, Izbicki JR . Correlation of thymic pathology with HLA in myasthenia gravis. Clin Immunol 1999; 91: 296–301.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Zabludovicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel

    Shahar Shelly, Nancy Agmon-Levin, Arie Altman & Yehuda Shoenfeld

  2. Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel

    Nancy Agmon-Levin, Arie Altman & Yehuda Shoenfeld

  3. Sackler Faculty of Medicine, Incumbent of the Laura Schwarz-Kip Chair for Research of Zabludowitz Center for Autoimmune Diseases, Tel-Aviv University, Tel-Aviv, Israel

    Yehuda Shoenfeld

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  1. Shahar Shelly
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  2. Nancy Agmon-Levin
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  4. Yehuda Shoenfeld
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Correspondence to Yehuda Shoenfeld.

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Shelly, S., Agmon-Levin, N., Altman, A. et al. Thymoma and autoimmunity. Cell Mol Immunol 8, 199–202 (2011). https://doi.org/10.1038/cmi.2010.74

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