title: Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft.
abstract: Excellent graft outcome has been reported for spousal-donor kidney transplantation. In husband-to-wife transplantation, however, a tendency toward inferior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplantations; three female recipients), actual graft survival is 100% (median observation time, 339 days). Five patients experienced early allograft rejection. In four transplant recipients, rejection was easily reversible by conventional antirejection therapy. In a multiparous recipient, however, mild interstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrolimus rescue therapy). The particular finding of polymorphonuclear neutrophils in peritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen suggested a role of antibody-mediated graft injury. Retrospective flow cytometry cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplantation lymphocytotoxic cross-match testing or screening for panel reactive antibodies. After transplantation, however, complement-fixing antibodies, also presumably triggered by reexposure to spousal-donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-mediated allograft rejection and led to the initiation of immunoadsorption therapy (14 sessions) with staphylococcal protein A. Selective removal of recipient IgG resulted in complete reversal of graft dysfunction. Our findings suggest that in husband-to-wife transplantation, donor-specific antibodies, presumably triggered by previous pregnancies, might occasionally induce sustained allograft dysfunction. Thus, in this particular setting, a detailed immunologic and histopathologic work-up regarding antibody-mediated allograft dysfunction is warranted because immunoadsorption may be a highly effective treatment modality.
authors.affiliation: Department of Internal Medicine III, Institute of Clinical Pathology, Institute of Immunology, University of Vienna, Austria. georg.boehmig@nephro.imed3.akh-wien.ac.at
authors.forename: G A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: H
authors.initials: H
authors.lastname: Regele
authors.forename: M D
authors.initials: MD
authors.lastname: Säemann
authors.forename: M
authors.initials: M
authors.lastname: Exner
authors.forename: W
authors.initials: W
authors.lastname: Druml
authors.forename: J
authors.initials: J
authors.lastname: Kovarik
authors.forename: W H
authors.initials: WH
authors.lastname: Hörl
authors.forename: G J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: B
authors.initials: B
authors.lastname: Watschinger
mesh_terms: D000917:Antibody Formation; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D003181:Complement C4 / Q000032:analysis; D015935:Complement C4b; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D010298:Parity; D010446:Peptide Fragments / Q000032:analysis; D011247:Pregnancy; D012189:Retrospective Studies; D018454:Spouses; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D000961:Antilymphocyte Serum; D003181:Complement C4; D006680:HLA Antigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D016559:Tacrolimus