title: A case of severe C4d-positive kidney allograft dysfunction in the absence of histomorphologic features of rejection.
abstract: Acute antibody-mediated (humoral) renal allograft rejection has emerged as a clinicopathological entity that carries a poor prognosis. Its diagnosis is based on typical pathohistologic features, serologic detection of donor-specific alloantibodies and the immunohistochemical finding of endothelial deposits of the complement split product C4d. We herein report a case of severe antibody-mediated graft injury after spousal-donor kidney transplantation. Despite an increased risk for humoral presensitization in the female recipient (three previous pregnancies), donor-specific alloantibodies were not detectable before transplantation. After initial graft function, severe graft dysfunction occurred one week after transplantation. A renal biopsy revealed no histomorphologic features of rejection. However, immunohistochemical detection of diffuse C4d deposits along peritubular capillaries suggested acute humoral rejection. The diagnosis of antibody-mediated rejection was confirmed by the detection of de-novo production of anti-donor alloantibodies. Graft dysfunction was resistant to high dose steroids or antilymphocyte antibody therapy. However, a recovery of graft function could be achieved by antibody elimination using immunoadsorption therapy. This case reinforces the high diagnostic value of C4d staining. In severe graft dysfunction humoral immune mechanisms should be considered, even when histopathologic features of humoral rejection are completely absent.
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Antje
authors.initials: A
authors.lastname: Habicht
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Afshin
authors.initials: A
authors.lastname: Soleiman
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Bruno
authors.initials: B
authors.lastname: Watschinger
authors.forename: Kurt
authors.initials: K
authors.lastname: Derfler
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000328:Adult; D003181:Complement C4; D015935:Complement C4b; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D010446:Peptide Fragments; D018454:Spouses; D014019:Tissue Donors
chemical_list: D003181:Complement C4; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d