Diminished regulatory T cells in cutaneous lesions of thymoma‐associated multi‐organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course

Summary Thymoma‐associated multi‐organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft‐ versus ‐host (GVH)‐like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin‐infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma‐associated multi‐organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma‐associated multi‐organ autoimmunity. Histopathological findings of thymoma‐associated multi‐organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (T regs ) is reduced in cutaneous lesions and CD8 + cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma‐associated multi‐organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4 + cells in patients with thymoma‐associated multi‐organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin‐infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma‐associated multi‐organ autoimmunity might be induced by self‐reactive cytotoxic T lymphocytes under the diminished suppressive capacity of T regs .