title: Sequential analysis of donor-specific antibodies and pathological findings in acute antibody-mediated rejection in a rat renal transplantation model.
abstract: Alloantibodies contribute significantly to renal transplant rejection by activation of complement and various cytokines with a variety of effector cells, and are a major cause of allograft loss. Although there is clinical evidence of antibody- and complement-mediated injury in renal transplantation, the mechanism of antibody-mediated rejection remains largely unknown. In order to understand the sequential production of antibodies and complement components, we presensitized recipient rats by skin transplantation. Anti-donor-specific IgG levels reached a maximum 2 weeks following presensitization after which the rats underwent renal transplantation from the same donor strain. We then evaluated sequential pathological findings based on the Banff classification and several factors related to graft rejection. In this presensitized model, peritubular capillaries were already dilated and stained for C4d. Neutrophil and mononuclear cell infiltration in these capillaries was detected beginning 2 h after transplantation. Donor-specific antibody IgG levels decreased rapidly and anti-IgG antibody stained glomerular and peritubular capillaries in the grafts beginning 2 h after transplantation. Additionally, several cytokines and complement components showed marked changes in the presensitized group. Thus, in the donor-specific presensitized recipient, alloantibodies and complement were activated immediately after transplant. C4d deposition in peritubular capillaries appears to be a key factor for the diagnosis of antibody-associated rejection.
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kohei
authors.forename: Tatsu
authors.initials: T
authors.lastname: Tanabe
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Omoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015935:Complement C4b / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D023421:Models, Animal; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation; D016019:Survival Analysis; D014019:Tissue Donors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d