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Published on: May 2, 2013
Influence of donor C3 allotype on late renal-transplantation outcome
Katherine M Brown1, Elli Kondeatis, Robert W Vaughan
1Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, United Kingdom.
Insights
Donor kidney C3F alleles improve long-term graft survival and function in C3S/S recipients. This suggests functional differences between C3F and C3S alleles in kidney transplantation outcomes.
Area of Science:
- Immunology
- Transplantation Science
- Genetics
Background:
- The complement system is crucial for immune responses.
- Human C3 protein has two main allotypes, F (fast) and S (slow), influencing inflammatory disease.
- This study investigates the impact of C3 allotypes on kidney graft outcomes.
Purpose of the Study:
- To determine the influence of donor C3 allotypes (F and S) on late renal-graft survival and function.
- To analyze the association between C3F/S polymorphism and clinical outcomes in kidney transplant recipients.
Main Methods:
- Determined C3 allotypes in 662 adult kidney donor-recipient pairs (1993-2002).
- Correlated C3F/S polymorphism with demographic and clinical outcome data.
- Median follow-up was 3.3 years.
Main Results:
- Graft survival was significantly better for kidneys from C3F/F or C3F/S donors compared to C3S/S donors (P=0.05).
- Hazard ratio for graft loss was 2.21 for C3S/S kidneys versus C3F/F or C3F/S kidneys (P=0.04).
- Graft function was significantly better for C3F/F or C3F/S donor kidneys (P<0.001).
Conclusions:
- Donor renal cell C3 allele expression differentially affects late graft outcome.
- In white C3S/S recipients, C3F/F or C3F/S donor kidneys showed significantly better long-term outcomes than C3S/S donor kidneys.
- Findings suggest functional differences between C3F and C3S alleles.
Background:
The complement system has a critical role in both the innate and the adaptive immune responses. In humans, C3 exists as two main allotypes, F (fast) and S (slow), which are known to affect the incidence of inflammatory disease. We conducted a study to address the influence of these alleles on late renal-graft outcome.
Methods:
We determined the C3 allotypes of 662 pairs of adult kidney donors and recipients from 1993 through 2002 and then related C3F/S polymorphism status to demographic and clinical outcome data. The median length of follow-up was 3.3 years.
Results:
Analysis of 513 pairs of white donors and recipients identified 113 C3S/S recipients of a C3S/F or a C3F/F kidney and 179 C3S/S recipients of a C3S/S kidney. Graft survival was significantly better with a C3F/F or C3F/S donor allotype than a C3S/S allotype (P=0.05). The hazard ratio for graft loss of C3S/S kidneys, as compared with C3F/F or C3F/S kidneys, was 2.21 (95 percent confidence interval, 1.04 to 4.72; P=0.04). The graft function of C3F/F or C3F/S donor kidneys was significantly better than that of C3S/S donor kidneys (P<0.001). The effect of the C3F allele was specific to recipients who did not themselves possess this allele. Multivariate analysis excluded effects of other factors known to influence graft outcome.
Conclusions:
Expression of C3 alleles by donor renal cells appears to have a differential effect on late graft outcome. Among white C3S/S recipients, receipt of a C3F/F or C3F/S donor kidney, rather than a C3S/S donor kidney, is associated with a significantly better long-term outcome. These findings suggest that the two alleles have functional differences.
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