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Molecular analysis of C3 allotypes related to transplant outcome in human renal allografts
P A Andrews1, J E Finn, P W Mathieson
1Department of Nephrology, UMDS, Guy's Hospital, London, United Kingdom.
Insights
The C3F allele, a form of the third complement component (C3), may increase the risk of kidney transplant dysfunction. This allele was linked to poorer graft function, but not graft loss, in transplant recipients.
Area of Science:
- Immunogenetics
- Nephrology
- Transplantation
Background:
- The third component of complement (C3) has two allotypes: C3S and C3F.
- The C3F allele is associated with autoimmune and kidney inflammatory diseases.
- Previous studies suggested a link between C3F and renal graft loss.
Purpose of the Study:
- To investigate the association between the C3 S/F polymorphism and outcomes in renal transplantation.
- To determine if the C3F allele influences graft loss or dysfunction after kidney transplantation.
Main Methods:
- Analysis of the C3 S/F polymorphism in 183 donor-recipient pairs undergoing renal transplantation.
- Assessment of graft loss and dysfunction (serum creatinine > 150 mumol/L) over a 14-month follow-up period.
- Statistical analysis to determine the relative risk associated with the C3F allele.
Main Results:
- Graft loss was not significantly associated with the C3F allele.
- The C3F allele significantly predicted an increased risk of graft dysfunction (relative risk = 1.4, P < 0.05).
- The C3F allele predisposed to dysfunction when present in either the donor or recipient, with a potential dose-dependent effect.
Conclusions:
- The C3F allele may be a susceptibility factor for allograft injury and dysfunction after kidney transplantation.
- The C3F allele is linked to increased risk of kidney transplant dysfunction, independent of graft loss.
- Further research into the mechanisms underlying C3F-associated allograft injury is warranted.
Abstract:
The third component of complement (C3) exists in two main allotypic forms, C3S and C3F, which can be distinguished at the molecular level using a variation of the polymerase chain reaction. An increased frequency of the C3F allele has been noted in a number of autoimmune and inflammatory conditions affecting the kidney, including systemic vasculitis, IgA nephropathy, and type II mesangiocapillary nephritis. Recently, in an unrelated study, we found (with small numbers) an increased incidence of graft loss associated with the presence of the C3F allele. To further assess this, we analyzed the S/F polymorphism in 183 donor-recipient pairs of patients undergoing renal transplantation. Forty-one of 183 grafts were lost, but graft loss was not associated with the C3F allele over 14-month follow-up. However, the presence of the C3F allele predicted an increased risk of graft dysfunction (defined as serum creatinine > 150 mumol/L): 61/105 versus 36/78, with a relative risk of 1.4 (P < 0.05). The C3F allele predisposed toward graft dysfunction when present in either donor or recipient. The presence of two C3F alleles gave a relative risk for graft dysfunction of 1.8, suggesting a dose-dependent effect, although numbers were small. The presence of the C3F allele was not significantly correlated with the number of rejection episodes, serum creatinine, or duration of primary nonfunction. These findings suggest that C3F may be a susceptibility allele for allograft injury. Possible mechanisms for this association are discussed.