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.
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.
Authors: Neil E Jenkins; Tabitha W Mwangi; Moses Kortok; Kevin Marsh; Alister G Craig; Thomas N Williams Journal: Clin Infect Dis Date: 2005-11-08 Impact factor: 9.079
Authors: W M Howell; P J Pead; F W Shek; M J Rose-Zerilli; T Armstrong; C D Johnson; D R Fine; J P Iredale; A C Bateman Journal: J Clin Pathol Date: 2005-06 Impact factor: 3.411
Authors: A Pettersson; X-C Wu; C Ciumas; H Lian; V Chirsky; Y-M Huang; B Bjelke; H Link; B-G Xiao Journal: Clin Exp Immunol Date: 2004-09 Impact factor: 4.330
Authors: Bjarte Fosby; Sigrid Næss; Johannes R Hov; James Traherne; Kirsten M Boberg; John Trowsdale; Aksel Foss; Pål-Dag Line; Andre Franke; Espen Melum; Helge Scott; Tom H Karlsen Journal: World J Gastroenterol Date: 2014-04-14 Impact factor: 5.742