RESUMEN
A prospective final crossmatch with patient serum and donor lymphocytes using the complement-dependent cytotoxicity assay to identify any performed anti-donor antibody is required for kidney transplantation. The presence of pre-existing antibody may lead to hyperacute rejection of the transplanted kidney. Certain anti-donor antibodies have previously been shown to be ineffective in promoting hyperacute rejection, such as IgM autoantibodies and non-specific IgM lymphocytotoxic antibodies. In this report, we present evidence that IgM HLA alloantibody specific to the donor does not lead to hyperacute rejection and produces graft survival results equivalent to transplants with negative pre-transplant final crossmatches. Forty-eight (48) of 402 patients transplanted over and 8 yr period were transplanted across a positive final crossmatch due to IgM antibodies alone. Three patients exhibited IgM autoantibodies and 26 patients demonstrated non-specific IgM antibodies to lymphocytes. In 15 patients, following a detailed serum screening analysis, a significant correlation (r > 0.9, p < 0.001) was observed between HLA Class I antigens and the presence of corresponding IgM alloantibodies. Five of these patients were subsequently transplanted despite a positive final crossmatch that was clearly demonstrated to be the result of IgM alloantibody to donor HLA Class I specificities. All of these patients continue to have graft function. These results suggest that hyperacute rejection is not mediated by any type of IgM antibody to donor lymphocytes and that kidney transplantation when only IgM antibody is present against donor lymphocytes represents a reasonable opportunity for a safe transplant and successful long-term graft survival.
Asunto(s)
Autoanticuerpos/análisis , Antígenos de Histocompatibilidad Clase I/análisis , Inmunoglobulina M/análisis , Isoanticuerpos/análisis , Trasplante de Riñón/inmunología , Inmunología del Trasplante/inmunología , Ditiotreitol , Femenino , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad , Humanos , Inmunoglobulina G/análisis , MasculinoAsunto(s)
Trasplante de Riñón/inmunología , Donantes de Tejidos , Adulto , Cadáver , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Retinopatía Diabética , Femenino , Supervivencia de Injerto/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de TiempoAsunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/aislamiento & purificación , ADN Viral/sangre , Trasplante de Riñón/fisiología , Secuencia de Bases , Citomegalovirus/genética , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/fisiopatología , ADN Viral/genética , Diagnóstico Diferencial , Fiebre/etiología , Rechazo de Injerto , Humanos , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa/métodos , Estudios ProspectivosRESUMEN
A human umbilical vein endothelial cell (EC)/monocyte (MC) coculture system was used to dissect cell:cell interactions associated with production of procoagulant activity (PCA) in response to two common stimuli of intravascular coagulation in vivo (LPS and immune complexes). We found that the presence of MC at a ratio of 1 MC:10 EC increased the sensitivity of EC to LPS by 4 logs and the maximal response approximately 20-fold. Aggregated IgG alone did not stimulate the system, but in the presence of small amounts of LPS (1 to 10 ng/ml) aggregated IgG was a powerful stimulus. More than 90% of the PCA was tissue factor as shown by clotting studies and mRNA analysis. PCA was not produced by either cell alone under the conditions of study, but was produced in large amounts when the EC and MC were cocultured. The supernatant from the coculture stimulated virgin EC, but not MC, to synthesize tissue factor. The major factor in the supernatant was IL-1 beta as shown by measuring IL-1 beta, IL-1 alpha, and TNF-alpha in supernatants and by blocking the production of PCA by preincubation of supernatants with anti-cytokine antibodies. Small amounts of TNF-alpha were present in the supernatant but anti-TNF-alpha did not inhibit PCA production. Studies using recombinant cytokines established that IL-1 beta was the most potent of the cytokines tested, that cytokines potentiated each other, and that the results could be explained in quantitative terms by the amounts of IL-1 beta measured. These data emphasize that cell:cell interactions are likely to modulate procoagulant events in vivo in the presence of both LPS and immune complexes, and that IL-1 beta may be an important cytokine in these events.