title: Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies.
abstract: Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1) was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%,p= 0.002). Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120μmol/L), 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77) versus 16.9% (30/178),p= 0.0187). A better understanding of this antigenic target will improve long-term allograft survival.
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China.
authors.forename: Xuli
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China; Research Laboratory of Blood Transfusion, Blood Center of Guizhou Province, Guizhou 550002, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.affiliation: Transplantation Center, The Third Xiangya Hospital of Central South University, Hunan 410013, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Ming
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Hunan 410008, China; The Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province, Hunan 410006, China.
authors.forename: Yizhou
authors.identifier: 0000-0002-9261-1161
authors.initials: Y
authors.lastname: Zou
mesh_terms: D064591:Allografts / Q000276:immunology; D000941:Antigens / Q000097:blood*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D047468:Immunoprecipitation; D053556:Keratin-1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G; D053556:Keratin-1; D011994:Recombinant Proteins; C087589:anti-endothelial cell antibody