title: Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course.
abstract: 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).
authors: Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: T
authors: T
authors: Hanafusa
authors: H
authors: H
authors: Azukizawa
authors: S
authors: S
authors: Kitaba
authors: H
authors: H
authors: Murota
authors: N
authors: N
authors: Umegaki
authors: M
authors: M
authors: Terao
authors: S
authors: S
authors: Sano
authors: T
authors: T
authors: Nakagiri
authors: M
authors: M
authors: Okumura
authors: I
authors: I
authors: Katayama
mesh_terms: D000328:Adult; D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D006801:Humans; D018655:Lymphocyte Count; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology; D013945:Thymoma / Q000276:immunology* / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment