title: Blood group antigen-targeting peptide suppresses anti-blood group antibody binding to antigen in renal glomerular capillaries after ABO-incompatible blood reperfusion.
abstract: BACKGROUND
  Antibody-mediated rejection after ABO-incompatible kidney transplantation (ABO-I KTx) is a major barrier to transplantation success. The advent of immunosuppressive therapy has markedly improved graft survival in ABO-I KTx. However, compared with normal KTx, clinical conditions during ABO-I KTx are difficult to control because of overimmunosuppression. To reduce the need for immunosuppression, we aimed to develop a novel blood group antigen-neutralizing therapy.
  
  
  METHODS
  We screened for an ABO blood group antigen-targeting peptide (BATP) by screening of T7 phage-displayed peptide library. After screening, hemagglutination inhibition assays, enzyme-linked immunosorbent assay, and cytotoxicity assay were used to analyze the blood group antigen-blocking effect and toxicity of BATP. We also tested the inhibitory effects on anti-blood group antibody binding in normal human kidney tissues blocked with BATP and excised kidneys perfused ex vivo with BATP.
  
  
  RESULTS
  We identified six peptide sequences that efficiently suppressed hemagglutination of red blood cells by anti-ABO blood group antibodies and binding of these antibodies to ABO histo-blood group antigens in kidney tissues. Surprisingly, ex vivo perfusion of BATP in kidneys excised from renal cell carcinoma patients caused significant suppression of anti-blood group antibody binding to antigen and IgG and IgM deposition in renal glomerular capillaries after ABO-I blood reperfusion.
  
  
  CONCLUSIONS
  These data indicate that A/B blood group antigens on red blood cells and in kidney tissues may be neutralized by BATP. This approach may enable the development of a novel blood group antigen-neutralizing therapy to overcome the challenges of ABO-I KTx.
authors.affiliation: Department of Advanced Transplantation and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoneyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tobisawa
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kengo
authors.initials: K
authors.lastname: Imanishi
authors.forename: Teppei
authors.initials: T
authors.lastname: Okamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Tokui
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Kudo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoneyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kamimura
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D001789:Blood Group Antigens / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000276:immunology*; D002196:Capillaries / Q000276:immunology* / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D007075:Immunoglobulin M / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D010455:Peptides / Q000502:physiology*; D015424:Reperfusion
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001789:Blood Group Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides