Thymectomy and systemic lupus erythematosus (SLE).
Dear Sir The thymus plays a crucial role in the context of cellmediated immunity in the differentiation of T lymphocytes, not only during the embryogenesis and fetal period but also during the adulthood, even after its involution 1,2,3. It has been proved, indeed, that thymectomy in adult rat entails a decrease of the T-lymphocite response to mitogens and eventually its abolition 4,5,6. The removal of the thymus can decrease the activity of T-helper cells but in the same time it might enhance the activity of T-suppressor whose function is depressed in autoimmune diseases 7. The therapeutic role of thymectomy is proved in Myasthenia Gravis even if the exact mechanism underlying its effect remains largely unknown. The role of thymectomy as a treatment of autoimmune diseases other than Myasthenia Gravis (i.e. sistemic lupus erythematosus, rheumatoid arthritis, autoimmune hemolytic anemia, multiple sclerosis) has been investigated but the results of these studies are questionable 7. Our aim is to evaluate the role of thymectomy in order to clarify whether it may be regarded not just as therapeuytic, but, on the contrary, as a factor paving the way to the onset of autoimmune diseases. Therefore, the relevant literature has been taken into account along our study. Thymus has an important role in regulating immune reaction through its control on T-cell differentiation of both T-helper and T-suppressor/cytotoxic cells. That is the reason why thymectomy produces a shift in autoimmune diseases with disregulation of the immune networks2. After thymectomy, indeed, an induction and an acceleration of autoimmune processes has been observed. A relevant work focusing on those mechanisms was written by Gerli et al1 . In their work, the authors consider the long term immunologic effects of therapeutic thymectomy in patients with Myasthenia Gravis comparing 16 patients with Myasthenia Gravis and previous Thymectomy (at least 8 years before), 6 patients with Myasthenia Gravis and recent Thymectomy (<1year) and 13 with Myasthenia Gravis non Thymectomized and 32 healthy subjects used as control. The study shows that the long term thymectomized patients had mild T-cell lymphopenia and an expansion of CD4+ and CD8+ cells. These serologic abnormalities were not detectable in not and recently thymectomized patients. Myasthenia Gravis and SLE are autoimmune disorders. They have positivity for antinuclear antibodies (ANA) and thymus hyperplasia. SLE is characterized by an alteration of the immune system that involves B cells and T lymphocites, resulting in polyclonal B cell activation and autoantybody production. The thymus deletes self-reactive T-cells with high avidity T-cell receptors for self antigens expressed in the thymus 8,9. This, hence, means that thymus has a protective role against autoimmunity. The prevalence of SLE in pts with Myasthenia Gravis has been reported 0,2%-2,7% 10. Cases in which the SLE has developed after thymectomy for Myasthenia Gravis have been reported in the literature, but there are also cases in which SLE developed before thymectomy in pts with both SLE and MG. Iwadate at al reported from a review of the literature in a period of 40 years (1963- 2004) 21 patients in whom LES developed after thymectomy. Their ages ranged from 11 to 66 years (mean 40.4 years) with SLE developing from 2 months to 13 years (mean 4.9 years) after thymectomy. Polyarthritis was the most common manifestation of SLE 11. The proof that thymectomy can facilitate the development of SLE can be traced in the cases reported by the literature. The prevalence of SLE among patients with thymoma varies between 1,5 and 10% 12. Boonen et al identified in a period of 20 years (1975-1998) 18 new cases of thymoma and SLE. In 39% of the patients SLE was diagnosed before detection of thymoma. In 33% of the patients, thymoma and SLE was found simultaneously and in 28% SLE was discovered after thymoma. In five cases thymectomy had no clear effect on SLE. In two cases an exacerbation was reported and in one case SLE was attenuated 11,13. However, Vaiopoulos et al 14 described in a series of 28 patients with both LES and Myasthenia Gravis, 17 cases in which LES developed before thymectomy.


CONCLUSIONS
Thymectomy may thus be a precipitating factor for the development of SLE due to the loss of central tolerance and the overproduction of antibodies. Therefore, after a thymectomy, it is important to perform a timely follow up of the patient.
Alessandra
A
Panarese
Vito
V
D'Andrea
Daniele
D
Pironi
Angelo
A
Filippini
D019317:Evidence-Based Medicine; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000209:etiology*; D009157:Myasthenia Gravis / Q000601:surgery; D012307:Risk Factors; D013934:Thymectomy / Q000009:adverse effects*; D013945:Thymoma / Q000601:surgery; D013953:Thymus Neoplasms / Q000601:surgery; D013997:Time Factors