Adhesion molecule polymorphisms in chronic renal allograft failure

Kidney Int. 1999 May;55(5):1977-82. doi: 10.1046/j.1523-1755.1999.00427.x.


Background: Chronic allograft failure (CAF) is a major cause of late graft loss in renal transplantation. Up-regulation of adhesion molecules has been demonstrated in renal allograft biopsies during both acute and chronic rejection, and these molecules are known to regulate leukocyte migration into the graft.

Methods: A single-center retrospective study was performed between 1985 and 1996 on renal transplant recipients who developed CAF. Genotyping was performed for five polymorphisms in intercellular adhesion molecule-1 (ICAM-1), E-selectin, and L-selectin. Frequency data for the polymorphisms in the CAF group (N = 62) and their matched donors, where available (N = 33), were compared with a group of recipients with graft survival of more than 10 years (N = 110) and a group of United Kingdom (UK) controls (N = 101).

Results: A variant allele in exon 4 of ICAM-1 (R241) was more common in the CAF recipients compared with both long-term survivors and UK controls (19.4 vs. 10.0 and 9.4%, P = 0.015 and 0.025). In addition, stratification by time to graft failure caused by CAF revealed more rapid failure in the presence of another ICAM-1 variant in the recipient (E469) in exon 6 (P = 0.033).

Conclusions: ICAM-1 polymorphisms may represent a predetermined genetic risk factor for CAF. The polymorphism in exon 4 is in the Mac-1 binding site, and that in exon 6 is in the fifth immunoglobulin-like domain. Potential mechanisms of action of ICAM-1 variants in CAF include an alteration of activity as an adhesion molecule, altered costimulation, or a minor histocompatibility antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cell Adhesion / immunology
  • Cell Adhesion Molecules / genetics*
  • E-Selectin / genetics
  • Graft Rejection / genetics*
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Kidney / blood supply
  • Kidney / chemistry
  • Kidney / surgery
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • L-Selectin / genetics
  • Leukocytes / cytology
  • Polymorphism, Genetic*
  • Renal Circulation / physiology
  • Reperfusion Injury / genetics
  • Retrospective Studies
  • Survival Analysis


  • Cell Adhesion Molecules
  • E-Selectin
  • Intercellular Adhesion Molecule-1
  • L-Selectin