2108 BLOOD GROUP ANTIGEN-TARGETING PEPTIDE SUPPRESSES ANTI-BLOOD GROUP ANTIBODY BINDING TO ANTIGEN IN RENAL GLOMERULAR CAPILLARIES AFTER ABO-INCOMPATIBLE BLOOD REPERFUSION

Abstract

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Renal Vascular Surgery1 Apr 20132108 BLOOD GROUP ANTIGEN-TARGETING PEPTIDE SUPPRESSES ANTI-BLOOD GROUP ANTIBODY BINDING TO ANTIGEN IN RENAL GLOMERULAR CAPILLARIES AFTER ABO-INCOMPATIBLE BLOOD REPERFUSION Tohru Yoneyama, Shingo Hatakeyama, Yuki Tobisawa, Hayato Yamamoto, Kengo Imanishi, Teppei Okamoto, Noriko Tokui, Naoki Sugiyama, Yuichiro Suzuki, Shigemasa Kudo, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Noritaka Kamimura, Michiko N Fukuda, and Chikara Ohyama Tohru YoneyamaTohru Yoneyama Hirosaki, Japan More articles by this author , Shingo HatakeyamaShingo Hatakeyama Hirosaki, Japan More articles by this author , Yuki TobisawaYuki Tobisawa Hirosaki, Japan More articles by this author , Hayato YamamotoHayato Yamamoto Hirosaki, Japan More articles by this author , Kengo ImanishiKengo Imanishi Hirosaki, Japan More articles by this author , Teppei OkamotoTeppei Okamoto Hirosaki, Japan More articles by this author , Noriko TokuiNoriko Tokui Hirosaki, Japan More articles by this author , Naoki SugiyamaNaoki Sugiyama Hirosaki, Japan More articles by this author , Yuichiro SuzukiYuichiro Suzuki Hirosaki, Japan More articles by this author , Shigemasa KudoShigemasa Kudo Hirosaki, Japan More articles by this author , Takahiro YoneyamaTakahiro Yoneyama Hirosaki, Japan More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto Hirosaki, Japan More articles by this author , Takuya KoieTakuya Koie Hirosaki, Japan More articles by this author , Noritaka KamimuraNoritaka Kamimura Hirosaki, Japan More articles by this author , Michiko N FukudaMichiko N Fukuda La Jolla, CA More articles by this author , and Chikara OhyamaChikara Ohyama Hirosaki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2017AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Antibody (Ab)-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 (HA) inhibition assays, ELISA 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 Ab binding in normal human kidney tissues blocked with BATP and excised kidneys perfused ex vivo with BATP. RESULTS We identified 6 peptide sequences that efficiently suppressed HA of red blood cells by anti-A or -B antigen Abs. Most effective peptide is RPRNPNK and named as BATP. Cytotoxicity of BATP against primary culture of blood type O human kidney glomerular capillary microvascular endothelial cells (HGMEC) was very low. BATP bound to peritubular and microvascular endothelia in type A and B kidney tissues but not in type O kidney tissues. BATP significantly inhibited the reactivity of anti-A and B Abs against A and B histo-blood group antigens expressed in glomerular capillaries as well as peritubular and microvascular endothelia. 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, IgG and IgM deposition in renal glomerular capillaries after ABO-I blood reperfusion (shown in figure). 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. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e864 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tohru Yoneyama Hirosaki, Japan More articles by this author Shingo Hatakeyama Hirosaki, Japan More articles by this author Yuki Tobisawa Hirosaki, Japan More articles by this author Hayato Yamamoto Hirosaki, Japan More articles by this author Kengo Imanishi Hirosaki, Japan More articles by this author Teppei Okamoto Hirosaki, Japan More articles by this author Noriko Tokui Hirosaki, Japan More articles by this author Naoki Sugiyama Hirosaki, Japan More articles by this author Yuichiro Suzuki Hirosaki, Japan More articles by this author Shigemasa Kudo Hirosaki, Japan More articles by this author Takahiro Yoneyama Hirosaki, Japan More articles by this author Yasuhiro Hashimoto Hirosaki, Japan More articles by this author Takuya Koie Hirosaki, Japan More articles by this author Noritaka Kamimura Hirosaki, Japan More articles by this author Michiko N Fukuda La Jolla, CA More articles by this author Chikara Ohyama Hirosaki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...