Thymus pathology observed in the MGTX trial

Annals of the New York Academy of Sciences

Volumn 1275, Issue 1, 2012, Pages 92-100

  Marx, Alexander ^a   Pfister, Frederik ^a   Schalke, Berthold ^c   Nix, Wilfred ^d   Ströbel, Philipp ^a,b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^d JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

CD23; Involution; Morphometry; Thymectomy; Thymic atrophy; Thymitis

Indexed keywords

AUTOANTIBODY; AZATHIOPRINE; CHOLINERGIC RECEPTOR ANTIBODY; CHOLINESTERASE INHIBITOR; CORTICOSTEROID; IMMUNOGLOBULIN; PREDNISONE;

ARTICLE; HISTOPATHOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; MORPHOMETRICS; MYASTHENIA GRAVIS; ONSET AGE; PROSPECTIVE STUDY; QUALITY OF LIFE; SURGICAL TECHNIQUE; THYMECTOMY; THYMOMA; THYMUS; THYMUS DISEASE; THYMUS HYPERPLASIA;

EID: 84871593483     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2012.06799.x     Document Type: Article

References (60)

1. Sauerbruch, E.F. 1913. Thymektomie bei einem Fall von Morbus Basedow mit Myasthenie. Mitt. Grenzgeb. Med. Chir. 25: 746-765.
2. Blalock, A. 1944. Thymectomy in the treatment of myasthenia gravis: report of twenty cases. J. Thorac. Surg. 13: 316-339.
3. Sonett, J.R. & A. Jaretzki, 3rd. 2008. Thymectomy for nonthymomatous myasthenia gravis: a critical analysis. Ann. N. Y. Acad. Sci. 1132: 315-328.
4. Walker, M.B. 1934. Treatment of Myasthenia gravis with Physostigmine. Lancet I: 1200-1201.
5. Grob, D. & T. Namba. 1966. Corticotropin in generalized myasthenia gravis. Effect of short, intensive courses. JAMA 198: 703-707.
6. Mertens, H.G., F. Balzereit & M. Leipert. 1969. The treatment of severe myasthenia gravis with immunosuppressive agents. Eur. Neurol. 2: 321-339.
7. Arsura, E.L. et al. 1986. High-dose intravenous immunoglobulin in the management of myasthenia gravis. Archive. Inter. Med. 146: 1365-1368.
8. Skeie, G.O. et al. 2010. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur. J. Neurol. 17: 893-902.
9. Gilhus, N.E. et al. 2011. Myasthenia gravis: a review of available treatment approaches. Autoimmun. Dis. 2011: 847393.
10. Drachman, D.B. 1994. Myasthenia gravis. N. Engl. J. Med. 330: 1797-1810.
11. Shiono, H. et al. 2003. Scenarios for autoimmunization of T and B cells in myasthenia gravis. Ann. N. Y. Acad. Sci. 998: 237-256.
12. Giraud, M., C. Vandiedonck & H.J. Garchon. 2008. Genetic factors in autoimmune myasthenia gravis. Ann. N. Y. Acad. Sci. 1132: 180-192.
13. Aarli, J.A. 2008. Myasthenia gravis in the elderly: is it different Ann. N. Y. Acad. Sci. 1132: 238-243.
14. Fraisse, T. et al. 2007. Myasthenia gravis in the elderly. Diagnosis, comorbidity and course: 45 cases. Presse. Med. 36: 9-14.
15. Pedersen, E.G. et al. 2012. Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009. Europ. J. Neurol. Aug 10. doi:10.1111/j.1468-1331.2012.03850.x [Epub ahead of print].
16. Spengos, K. et al. 2008. Dropped head syndrome as prominent clinical feature in MuSK-positive Myasthenia Gravis with thymus hyperplasia. Neuromuscular Disord. 18: 175-177.
17. Kawaguchi, N. et al. 2007. Effects of thymectomy on late-onset myasthenia gravis without thymoma. Clin. Neurol. Neurosurg. 109: 858-861.
18. Tsuchida, M. et al. 1999. Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis. Ann. Thor. Surg. 67: 1563-1567.
19. Romi, F. et al. 2002. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. Eur. J. Neurol. 9: 55-61.
20. Marx, A. et al. 2010. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 43: 413-427.
21. Romi, F. et al. 2003. Disease severity and outcome in thymoma myasthenia gravis: a long-term observation study. Eur. J. Neurol. 10: 701-706.
22. de Perrot, M. et al. 2002. Prognostic significance of thymomas in patients with myasthenia gravis. Ann. Thor. Surg. 74: 1658-1662.
23. Tsinzerling, N. et al. 2007. Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology. J. Neurol., Neurosurg., Psychiatr. 78: 1109-1112.
24. Maggi, L. et al. 2008. Thymoma-associated myasthenia gravis: outcome, clinical and pathological correlations in 197 patients on a 20-year experience. J. Neuroimmunol. 201-202: 237-244.
25. Lucchi, M. et al. 2009. Association of thymoma and myasthenia gravis: oncological and neurological results of the surgical treatment. Eur. J. Cardio-Thoracic Surg. 35: 812-816; discussion 816.
26. Prokakis, C. et al. 2009. Modified maximal thymectomy for myasthenia gravis: effect of maximal resection on late neurologic outcome and predictors of disease remission. Annal. Thorac. Surg. 88: 1638-1645.
27. Hsu, H.S. et al. 2006. Thymoma is associated with relapse of symptoms after transsternal thymectomy for myasthenia gravis. Interact. Cardiovasc. Thorac. Surg. 5: 42-46.
28. Jaretzki, A., 3rd et al. 1988. "Maximal" thymectomy for myasthenia gravis. Results. J. Thorac. Cardiovasc. Surg. 95: 747-757.
29. Evoli, A. et al. 2003. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 126: 2304-2311.
30. Leite, M.I. et al. 2005. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Annal. Neurol. 57: 444-448.
31. Strobel, P. et al. 2008. The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens. J. Neuroimmunol. 201-202: 64-73.
32. Reinhardt, C. & A. Melms. 2000. Normalization of elevated CD4-/CD8- (double-negative) T cells after thymectomy parallels clinical remission in myasthenia gravis associated with thymic hyperplasia but not thymoma. Annal. Neurol. 48: 603-608.
33. Willcox, N. et al. 1991. The thymus in seronegative myasthenia gravis patients. J. Neurol. 238: 256-261.
34. Melms, A. et al. 1992. T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: heterogeneity of antigenic sites on the alpha-subunit. Annal. Neurol. 31: 311-318.
35. Melms, A. et al. 1993. Acetylcholine receptor-specific T cells are present in the normal immune repertoire. A study with recombinant polypeptides of the human acetylcholine receptor alpha-subunit. Annal. N. Y. Acad. Sci. 681: 310-312.
36. Wekerle, H. & U.P. Ketelsen. 1977. Intrathymic pathogenesis and dual genetic control of myasthenia gravis. Lancet 1: 678-680.
37. Leite, M.I. et al. 2007. Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status. Am. J. Pathol. 171: 893-905.
38. Le Panse, R. et al. 2010. Thymic remodeling associated with hyperplasia in myasthenia gravis. Autoimmunity 43: 401-412.
39. Nieto, I.P. et al. 1999. Prognostic factors for myasthenia gravis treated by thymectomy: review of 61 cases. Annal. Thorac. Surg. 67: 1568-1571.
40. Genkins, G. et al. 1975. Studies in myasthenia gravis: early thymectomy. Electrophysiologic and pathologic correlations. Am. J. Med. 58: 517-524.
41. Ponseti, J.M. et al. 2008. Influence of ectopic thymic tissue on clinical outcome following extended thymectomy in generalized seropositive nonthymomatous myasthenia gravis. Eur. J. Cardio-Thorac. Surg. 34: 1062-1067.
42. Ruckert, J.C. et al. 2003. Matched-pair comparison of three different approaches for thymectomy in myasthenia gravis. Surg. Endoscop. 17: 711-715.
43. Ruckert, J.C., M. Swierzy & M. Ismail. 2011. Comparison of robotic and nonrobotic thoracoscopic thymectomy: a cohort study. J. Thorac. Cardiovas. Surg. 141: 673-677.
44. Weksler, B. et al. 2012. Robot-assisted thymectomy is superior to transsternal thymectomy. Surg. Endoscop. 26: 261-266.
45. Afifi, A. et al. 2010. For neonates undergoing cardiac surgery does thymectomy as opposed to thymic preservation have any adverse immunological consequences Interact. Cardiovasc. Thorac. Surg. 11: 287-291.
46. Miller, J.F. 2011. The golden anniversary of the thymus. Nature reviews. Immunology 11: 489-495.
47. Wolfe, G.I. et al. 2003. Development of a thymectomy trial in nonthymomatous myasthenia gravis patients receiving immunosuppressive therapy. Annal. N. Y. Acad. Sci. 998: 473-480.
48. Newsom-Davis, J. et al. 2008. Status of the thymectomy trial for nonthymomatous myasthenia gravis patients receiving prednisone. Annal. N. Y. Acad. Sci. 1132: 344-347.
49. Aban, I.B. et al. 2008. The MGTX experience: challenges in planning and executing an international, multicenter clinical trial. J. Neuroimmunol. 201-202: 80-84.
50. Mori, T. et al. 2007. The distribution of parenchyma, follicles, and lymphocyte subsets in thymus of patients with myasthenia gravis, with special reference to remission after thymectomy. J. Thorac. Cardiovas. Surg. 133: 364-368.
51. Chiu, H.C. et al. 1987. Myasthenia gravis: population differences in disease expression and acetylcholine receptor antibody titers between Chinese and Caucasians. Neurology 37: 1854-1857.
52. Somnier, F.E. 2005. Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis. Neurology 65: 928-930.
53. Murai, H. et al. 2011. Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey. J. Neurol. Sci. 305: 97-102.
54. Kirchner, T. et al. 1986. Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis. Virch. Archiv. B, Cell Pathol. include. Molecul. Pathol. 52: 237-257.
55. Roxanis, I. et al. 2002. Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis. J. Neuroimmunol. 125: 185-197.
56. Levine, G.D. & J. Rosai. 1978. Thymic hyperplasia and neoplasia: a review of current concepts. Hum. Pathol. 9: 495-515.
57. Okabe, H. 1966. Thymic lymph follicles; a histopathological study of 1, 356 autopsy cases. Acta Pathol. Japonica. 16: 109-130.
58. Smith, S.M. & L.J. Ossa-Gomez. 1981. A quantitative histologic comparison of the thymus in 100 healthy and diseased adults. Am. J. Clin. Pathol. 76: 657-665.
59. Ferri, C. et al. 2006. Thymus alterations and systemic sclerosis. Rheumatology 45: 72-75.
60. Willcox, N. et al. 1989. Variable corticosteroid sensitivity of thymic cortex and medullary peripheral-type lymphoid tissue in myasthenia gravis patients: structural and functional effects. Qtly. J. Med. 73: 1071-1087.