RESUMO
We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on 'for cause'. Using enzyme-linked immunosorbent spot assays, we found interferon-γ production by indirect allorecognition in 45 of 119 total samples from the 65 patients. B-cells preferentially processed and presented donor alloantigens in samples from AMR patients. In a further 25 samples, B-cell-dependent allo-specific reactivity was shown by depletion of CD25(+) cells and these individuals had higher percentages of CD4CD25hi cells. In 21 samples, reactivity was shown by depletion of CD19(+) cells, associated with polarized cytokine production toward IL-10 after polyclonal activation by IgG/IgM. Overall, this shows a significant contribution by B-cells to indirect donor-specific T-cell reactivity in vitro in patients with AMR. Active suppression by distinct phenotypes of T- or B-cells in approximately half of the patients indicates that chronic AMR is not characterized by a universal loss of immune regulation. Thus, stratified approaches that accommodate the heterogeneity of cell-mediated immunity might be beneficial to treat graft dysfunction.
Assuntos
Linfócitos B/imunologia , Comunicação Celular , Rejeição de Enxerto/imunologia , Imunidade Humoral , Transplante de Rim/efeitos adversos , Rim/imunologia , Linfócitos T/imunologia , Linfócitos B/metabolismo , Biópsia , Células Cultivadas , Doença Crônica , ELISPOT , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/metabolismo , Humanos , Imunofenotipagem , Interferon gama/imunologia , Interferon gama/metabolismo , Testes de Liberação de Interferon-gama , Isoanticorpos/imunologia , Isoanticorpos/metabolismo , Isoantígenos/imunologia , Ativação Linfocitária , Fenótipo , Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
The increasing rate of implantable cardioverter defibrillator (ICD) implantation coupled with shared risk factors between lung cancer and ischemic cardiac disease means that the need for radiotherapy in cardiac device patients is set to become commonplace. We describe two cases referred to our electrophysiology service over a 6-month period. Both had been diagnosed with lung cancer in tissue directly posterior to a previously implanted ICD device. The cases highlight the risks to device function caused by ionizing radiation, the practical difficulties and ethical dilemmas of delivering radiotherapy to cardiac device patients safely and a novel setting for the use of a wearable defibrillator system.