The Effect Of Thymectomy On Autoimmune Diseases

Bone-marrow transplantation has recently been suggested as an optional treatment for severe autoimmune diseases [25], As there is a strong association between thymic pathology and autoimmunity, it is not surprising that thymectomy also might have a beneficial effect on the course of autoimmune diseases.

4.1. The Rationale Behind Thymectomy for the Treatment of Autoimmune Diseases

Since MG is the autoimmune disease most commonly found in patients with thymoma, literature reports focus on the pathogenesis of this disease in thymo-matous patients. Alterations in the thymus are found in about 80% of MG patients. When MG is associated with thymitis, the acetylcholine receptors on the my-oid cells trigger a classical antigen-driven immune reaction and the intrathymic production of acetylcholine receptor-specific autoantibodies [26]. Thymus cells from 82 out of 109 MG patients with serum acetylcholine receptor-specific autoantibodies secreted these antibodies in vitro [27]. On the other hand, in thymomas there is an expression of abnormal neurofilaments that share epitopes with the acetylcholine-receptor, and they trigger autoantigen-specific T-cell selection by molecular mimicry. Neither intratumor autoantibody production nor T-cell activation seems to occur in thymomas [26]. The isolation of similar acetylcholine receptor-specific T-cell clones from 2 MG thymomas and the presence of their minority isotypes also on antigen-presenting cells in the donors' tumors, further support the theory of active induction of specific T cells by thymomas, rather than failure to tolerize them against self antigens [28]. Therefore, it is only logical to speculate that removal of the thymus/thymoma might at least result in removal of the trigger of the disease, and thus lead to clinical improvement.

4.2. Clinical Outcome of Thymectomy in Autoimmunity

Thymectomy is most often used in MG patients, and as a rule of a thumb it should be offered to all MG patients unless they are older than 50 years of age, have purely ocular disease, minimal symptoms or juvenile myasthenia [29]. However, the nature of thymic involvement in the pathogenesis of MG affects the response to thymectomy: whereas 80% of the patients with thymic hyperplasia are expected to have significant clinical improvement or even complete remission after thymectomy, the response to thymectomy is disappointing in the presence of thymoma [30]. Similarly, thymectomy results in a good clinical response in patients with relapsing-remitting multiple sclerosis rather than patients with chronic-progressive disease [31]. Another condition in which thymectomy was found beneficial is ulcerative colitis: in a series of ulcerative colitis patients, thymectomy induced high percentage of remission, and decreased the anticolon antibody activity [32],

As opposed to either the clinical improvement or the no significant change after thymectomy, this procedure can also result in clinical deterioration. The best example is SLE that is which thymectomy is practically contraindicated [33]. Even though there are few reports of a good clinical outcome of thymec-tomized SLE patients [17, 34], the disease can either deteriorate [17] or even appear de novo (reviewed in [35]). Furthermore, as autoimmune diseases were found to appear in several cases after bonemarrow transplantation [36], a similar phenomenon occurs after thymectomy: whereas this procedure is used successfully for the treatment of one disease, a "disease switch" occurs and a new disease appears [37-38]. Examples include the appearance of pemphigus, SLE and antiphospholipid syndrome after thymectomy for another condition, usually MG.

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