title: A case of acute antidonor antibody-mediated humoral rejection after renal transplantation with specific consideration of serial graft biopsy histology.
abstract: A 61-year-old-woman with end-stage renal disease caused by IgA nephropathy received living unrelated kidney transplantation from her husband in February 2001. Pre-transplant donor-specific T- and B-cell cross-match was negative. Immunosuppressive treatment consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), methylprednisolone (MP) and antilymphocyte globulin (ALG). The kidney functioned immediately after kidney transplantation. On post-operative day 9, the level of serum creatinine (S-Cr) rose from 1.1 to 1.5 mg/dL. The allograft biopsy specimen taken on the day revealed moderate accumulations of polymorphonuclear leucocytes in peritubular capillaries (PTCs), dilatation of PTCs and transplant glomerulitis, moderate to severe. Immunofluorescent study of a frozen section of the allograft biopsy specimen showed a strong, diffusely distributed endothelial staining pattern in PTCs for the stable complement split product C4d. Post-transplant donor-specific T- and B-cell cross-matches performed on post-operative day 13 were positive. From the allograft biopsy and the positive post-transplant donor-specific T- and B-cell cross-matching, acute humoral rejection (AHR) associated with the development of antidonor antibodies (ADA) was diagnosed. Plasma exchange (PE) treatment was initiated on day 11. After a total of 13 treatments of PE, donor-specific T- and B-cell cross-matches became negative and the biopsy performed on day 72 revealed mild transplant glomerulopathy without accumulation of polymorphonuclear leucocytes in PTCs or a C4d staining pattern in PTCs of immunofluorescence. The allograft functioned well and the creatinine level was 1.1 mg/dL 7 months post-transplant. This was a case of AHR after renal transplantation associated with the development of ADA, which was triggered by spousal-donor antigens. The presence of widespread C4d deposition in PTCs in renal allograft biopsies played a role in the diagnosis of AHR and the diagnosis was confirmed by positive donor-specific T- and B-cell cross-matches at the time of rejection, which were negative at pre-transplantation. Several treatments of PE were effective for resolving AHR in this case and the effect of PE in the treatment of AHR could be assessed by the degree of peritubular capillaritis (PTCitis) and C4d deposits in PTCs.
authors.affiliation: Department of Urology, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Michio
authors.initials: M
authors.lastname: Tokiwa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D000906:Antibodies / Q000097:blood*; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy; D003181:Complement C4 / Q000032:analysis; D015935:Complement C4b; D005260:Female; D005922:Glomerulonephritis, IGA / Q000601:surgery; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000473:pathology*; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010951:Plasma Exchange; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D003181:Complement C4; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d