Kok, J.L. (Julian) (2012) Lectin complement pathway gene profile in kidney transplantation. thesis, Medicine.
Full text available on request.Abstract
In kidney transplantation, complement activation was found to be induced by donor brain death, renal ischemia-reperfusion injury (IRI) and allograft rejection. The complement system is a part of the innate immune system and is involved in the clearance of immune complexes and forms an interface between adaptive and innate immunity. The lectin pathway is one of the complement activating pathways and acts by binding of mannose-binding lectins (MBLs) and/ or ficolins to carbohydrate structures on the cell surface. After binding of these lectins MBL associated serine proteases(MASPs) become activated and initiate a convertase cascade which finally leads to cell lysis. Single nucleotide polymorphisms (SNPs) in the genes encoding the lectin pathway proteins determine their functional activity and serum levels. In kidney transplantation, it has been shown that the lectin pathway plays a damaging role in the course of renal IRI and in allograft rejection. Therefore, the aim of this study was to investigate whether these functional polymorphisms would influence the clinical outcome after kidney transplantation. A total of 12 functional SNPs in the MBL2, FCN2 and MBL-associated serine proteases 2 (MASP2) genes of 1271 donor-recipient pairs were determined. Lectin genotypic variants were analyzed for association with primary non-function (PNF), delayed graft function (DGF), biopsy proven acute rejection, death-censored graft survival and patient survival. Multivariate analyses found no association of donor and recipient MBL2 and MASP2 genotype with allograft outcome. Analysis of separate functional SNPs and haplotypes in the FCN2 gene of the donor and recipient did not reveal an association with transplant outcome. Also, the joint effect of the MBL2 and FCN2 genotype was not associated with allograft outcome.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor: and Seelen M.A. M.D., PhD. and University Medical Center Groningen (UMCG) and Experimental Nephrology and Surgical Research Laboratory |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:58 |
| Last Modified: | 25 Jun 2020 10:58 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1888 |
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