Differential immunogenicity and clinical relevance of kidney compartment specific antigens after renal transplantation

J Proteome Res. 2010 Dec 3;9(12):6715-21. doi: 10.1021/pr1008674. Epub 2010 Nov 5.


To evaluate the pathogenic role of non-HLA antibodies after organ transplantation, 81 unique serum samples from renal transplant patients were analyzed by protein array technology on integrative genomics approach (Li, L.; et al. Proc. Natl. Acad. Sci. U.S.A. 2009, 106 (11), 4148-53; Higgins, J. P.; et al. Mol. Biol. Cell 2004, 15 (2), 649-56), validated by ELISA, and the results correlated with clinical relevance with time post-transplantation or post-transplant graft function. There was a significant association of de novo non-HLA antibodies with time post-transplantation (n = 1,785) and decline in graft function over the subsequent year (n = 105). There was an enrichment of immunogenic antigens in the renal cortex (p = 0.01) with post-transplant time, and for glomerular specific targets (p = 0.02) with decline in graft function. Two targets with very strong correlation in each category (AGT and SPDYA) were validated by customized ELISA assays in independent patient sera and their localization confirmed by immunohistochemistry. In conclusion, defined profiles of these non-HLA antibodies to renal cortical proteins develop with increasing length of engraftment, and may reflect the increasing recognition of altered localization or exposure of renal tubular and interstitial proteins, affected by advancing chronic nonimmune graft injury. The panel of non-HLA antibodies to glomerular targets is most interesting, as these corresponding antigenic targets may be important pathways in functional graft injury and could provide novel targets for drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensinogen / immunology
  • Angiotensinogen / metabolism
  • Antibodies / analysis
  • Antibodies / blood
  • Antibodies / immunology*
  • Antigens / immunology*
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Graft Rejection / immunology
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Humans
  • Immunohistochemistry
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / methods
  • Male
  • Microarray Analysis / methods
  • Proteomics / methods
  • Time Factors


  • AGT protein, human
  • Antibodies
  • Antigens
  • Cell Cycle Proteins
  • HLA Antigens
  • SPDYA protein, human
  • Angiotensinogen