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Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation
Published on: May 2, 2013
Identification of ICAM-1 polymorphism that is associated with protection from transplant associated vasculopathy
S Borozdenkova1, J Smith, S Marshall
1National Heart and Lung Institute, Imperial College School of Medicine, Royal Brompton and Harefield NHS Trust, Harefield, Middlesex, United Kingdom .
Insights
Gene variations in adhesion molecules, specifically ICAM-1 E-469 allele in donors, may protect against transplant-associated coronary disease (TxCAD) and allograft rejection in cardiac transplant recipients.
Area of Science:
- Immunology
- Transplantation Medicine
- Genetics
Background:
- Transplant-associated coronary disease (TxCAD) is a primary cause of late graft loss after cardiac transplantation.
- TxCAD is a complex condition influenced by both immunologic and non-immunologic factors.
- Understanding genetic predispositions in donors and recipients is crucial for preventing TxCAD.
Purpose of the Study:
- To investigate the association between gene polymorphisms in adhesion molecules (L-selectin, E-selectin, ICAM-1, PECAM) and the development of TxCAD.
- To analyze the role of these polymorphisms in donors and recipients of cardiac transplants.
- To assess the potential protective effects of specific alleles against allograft rejection.
Main Methods:
- Retrospective genotyping of 82 cardiac transplant patients, 96 donors, and 101 UK controls.
- Analysis of nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1, and PECAM using allele-specific PCR-SSP.
- Categorization of recipients based on TxCAD development (within 2 years) or absence (4.5-5 years).
Main Results:
- No significant association found between TxCAD and polymorphisms in E-selectin, L-selectin, or PECAM.
- Donors whose recipients did not develop TxCAD within 2 years showed a higher frequency of the ICAM-1 E-469 allele (63.8%) compared to TxCAD recipients (46.4%) and controls (47%).
- A decreased frequency of the ICAM-1 E469 allele correlated with an increased number of rejection episodes.
Conclusions:
- The ICAM-1 E-469 allele may play a protective role against TxCAD development.
- The presence of the ICAM-1 E469 allele in either donor or recipient appears to confer protection against allograft rejection.
- Further research into ICAM-1 polymorphism could inform strategies to prevent TxCAD and improve transplant outcomes.
Abstract:
Transplant associated coronary disease (TxCAD) is the main cause of late graft loss following cardiac transplantation. It is a multifactorial disease with immunologic and nonimmunologic components involved. This study was undertaken to analyze the gene polymorphism in adhesion molecules in donors and recipients and to investigate its potential association with the development of TxCAD. A total of 82 cardiac transplant patients, 96 donors and 101 UK controls, were genotyped retrospectively. Nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1, and PECAM were analyzed using allele-specific PCR-SSP assay. Recipients were selected on the basis of the development of TxCAD: patients who had developed TxCAD within 2 years after transplantation, and patients who did not have TxCAD within 4.5-5 years after transplantation. All recipients received CyA and azathioprine as a primary immunosuppression. Associations were assessed by using Fisher's exact test. No association was found between E-selectin, L-selectin, and PECAM allele or genotype frequencies and TxCAD. However, the donors whose recipients did not develop TxCAD at first 2 years had a significant increase of ICAM-1 E-469 allele compared with donors, whose recipients developed TxCAD (63.8% vs 46.4%, p = 0.042) and to UK controls (63.8% vs 47%, p = 0.04). Moreover, we found that the decreased frequency of ICAM E469 allele was associated with the increased number of rejection episodes. The 469 E/K polymorphism is in exon 6 and results in a change from glutamic acid to lysine in Ig-like domain 5 of ICAM-1, which is thought to affect interactions with LFA-1 and adhesion of B-cells. Our data suggest the presence of allele E469 ICAM-1 in either donor or recipient is protective against allograft rejection in a transplant setting.
