Assuntos
Cetuximab/farmacologia , Imunidade Inata/efeitos dos fármacos , Queratinócitos/imunologia , Panitumumabe/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Anticorpos Monoclonais/farmacologia , Receptores ErbB/imunologia , Humanos , Proteínas Tirosina Quinases/antagonistas & inibidoresAssuntos
Quimiocina CCL17/fisiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Adulto , Idoso , Citomegalovirus/genética , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/induzido quimicamente , DNA Viral/isolamento & purificação , Síndrome de Hipersensibilidade a Medicamentos/sangue , Feminino , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/fisiologia , Humanos , Interleucinas/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Infecções por Roseolovirus/induzido quimicamente , Ativação ViralRESUMO
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).
Assuntos
Autoimunidade/imunologia , Linfócitos T Reguladores/imunologia , Timoma/imunologia , Timoma/patologia , Adulto , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Contagem de Linfócitos , Psoríase/imunologia , Psoríase/patologia , Pele/imunologia , Pele/patologia , Dermatopatias/imunologia , Dermatopatias/metabolismo , Dermatopatias/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Timo/imunologia , Timo/patologia , Microambiente TumoralAssuntos
Compostos Azo/efeitos adversos , Benzenossulfonatos/efeitos adversos , Queilite/etiologia , Corantes/efeitos adversos , Cosméticos/efeitos adversos , Emolientes/efeitos adversos , Álcoois Graxos/efeitos adversos , Maleatos/efeitos adversos , Adulto , Queilite/diagnóstico , Feminino , Glicerídeos/efeitos adversos , Humanos , Testes do Emplastro , RecidivaRESUMO
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.