Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft

Excellent graft outcome has been reported for spousal-donor kidney transpla ntation. In husband-to-wife transplantation, however, a tendency toward inf erior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplant ations; three female recipients), actual graft survival is 100% (median obs ervation time, 339 days). Five patients experienced early allograft rejecti on. In four transplant recipients, rejection was easily reversible by conve ntional antirejection therapy. In a multiparous recipient, however, mild in terstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrollmus re scue therapy). The particular finding of polymorphonuclear neutrophils in p eritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen su ggested a role of antibody-mediated graft injury. Retrospective flow cytome try cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplan tation lymphocytotoxic crossmatch testing or screening for panel reactive a ntibodies. After transplantation, however, complement-fixing antibodies, al so presumably triggered by reexposure to spousal donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-media ted allograft rejection and led to the initiation of immunoadsorption thera py (14 sessions) with staphylococcal protein A. Selective removal of recipi ent IgG resulted in complete reversal of graft dysfunction. Our findings su ggest that in husband-to-wife transplantation, donor-specific antibodies, p resumably triggered by previous pregnancies, might occasionally induce sust ained allograft dysfunction. Thus, in this particular setting, a detailed i mmunologic and histopathologic work-up regarding antibody-mediated allograf t dysfunction is warranted because immunoadsorption may be a highly effecti ve treatment modality. (C) 2000 by the National Kidney Foundation, Inc.