Asunto(s)
Cetuximab/farmacología , Inmunidad Innata/efectos de los fármacos , Queratinocitos/inmunología , Panitumumab/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Anticuerpos Monoclonales/farmacología , Receptores ErbB/inmunología , Humanos , Proteínas Tirosina Quinasas/antagonistas & inhibidoresAsunto(s)
Quimiocina CCL17/fisiología , Síndrome de Hipersensibilidad a Medicamentos/etiología , Adulto , Anciano , Citomegalovirus/genética , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/inducido químicamente , ADN Viral/aislamiento & purificación , Síndrome de Hipersensibilidad a Medicamentos/sangre , Femenino , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/fisiología , Humanos , Interleucinas/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Infecciones por Roseolovirus/inducido químicamente , Activación ViralRESUMEN
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).
Asunto(s)
Autoinmunidad/inmunología , Linfocitos T Reguladores/inmunología , Timoma/inmunología , Timoma/patología , Adulto , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Humanos , Recuento de Linfocitos , Psoriasis/inmunología , Psoriasis/patología , Piel/inmunología , Piel/patología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/inmunología , Timo/inmunología , Timo/patología , Microambiente TumoralAsunto(s)
Compuestos Azo/efectos adversos , Bencenosulfonatos/efectos adversos , Queilitis/etiología , Colorantes/efectos adversos , Cosméticos/efectos adversos , Emolientes/efectos adversos , Alcoholes Grasos/efectos adversos , Maleatos/efectos adversos , Adulto , Queilitis/diagnóstico , Femenino , Glicéridos/efectos adversos , Humanos , Pruebas del Parche , RecurrenciaRESUMEN
A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-alphabeta receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN-alpha and -beta, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-alpha and -beta. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.