Corneal transplantation is the oldest, most common and usually the most successful type of solid tissue allograft. The acceptancc of corneal allografts compared to other categories of allografts is called immune privilege. However, some conditions rob the corneal allograft of its immune privilege and promote rejection, which remains the leading cause of corneal graft failure. The precise immune mechanism underlying graft failure is incompletely understood. While differences in human leukocyte antigen (HLA) molecules between donor and host contribute to the alloreactivity driving the donor-antihost response, the cytokine milieu consisting of molecules that promote and regulate the alloresponse after transplantation is also critical. Single nucleotide polymorph isms (SNPs) in the promoter and coding regions of cytokine genes are associated with differential levels of expression and therefore play an important role in transplantation immunology. Cytokines are integral components of an inflammatory response and there are several potential sources of cytokine release within the cornea and the anterior chamber. This project is a candidate gene association study, focusing on genes known to be involved in ocular immune privilege and the compromise thereof, in corneal transplant recipients at increased risk of rejection (i.e., 'high risk corneal transplantation). In view of their central roles in initiation and suppression of the inflammatory response, tumour necrosis factor alpha (Tufa), interleukin - IO (IL• I 0), interleukin- 17 ( IL-1 7), thrombospondin•1 (TSP-I), vascular endothelial growth factor-A (VEG F-A) and the glucocorticoid cortisol were investigated. All transplants had three-year follow-up and results were analysed by PHASE (maximum-likelihood) analysis is to determine haplotype frequencies. Significant association between two extended TNF-u haplotypes and corneal graft outcome was found: TCTGGA was associated with a decreased risk of cornea] graft failure (n=384, RR 0.04, Cl 002-0.671, P <0.05, Pc <0.05) and TCTAGA was associated with increased risk of failure (n=384, RH. 3.59, Cl 3.21-4.03, P <0.05, Pc <0.05). In addition, a significant association was observed between the 3-1ocus TSP-] haplotype ACA, and an increased risk of corn ca I graft failure (n==359, OR 2.27, 95% Cl 1.65-3.13, P<0.05, P, <0.05).
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:617796 |
| Date | January 2012 |
| Creators | Winton, Helen Louise |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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