P32 (RA6448)
The Influence of Donor C3 Allotype on Late Renal Transplant Outcome
KM Brown1, E Kondeatis1, RW Vaughan1, SP Kon2, CKT Farmer3, JD Taylor1, X
He4, A Johnston4, C Horsfield5, BJC Janssen5, P Gros5, W Zhou1, SH Sacks1 and NS
Sheerin1
1
Nephrology and Transplantation, 5th Floor Thomas Guy House, Guy's Hospital,
London, SE19 3AS, United Kingdom, 2King's College Hospital, Denmark Hill,
London, SE5 9RS, United Kingdom, 3Kent & Canterbury Hospital, Ethelbert Road,
Canterbury, CT1 3NG, United Kingdom, 4Clinical Pharmacology, Barts and the
London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom
and 5Department of Histopathology, Guy's and St Thomas' NHS Foundation Trust,
London, United Kingdom
The complement system plays a critical role in both innate and 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. This study addresses the
influence of these alleles on late renal graft outcome.
We determined the C3 allotype of 662 adult kidney transplants performed at Guy’s
Hospital between 1993-2002. Median patient follow up was 3.26 years. Both donor
and recipient were typed and the C3F/S polymorphism related to demographic and
clinical outcome data
Analysis of Caucasian recipients (n=513) identified 113 C3SS patients receiving a
C3SF or C3FF kidney and 179 C3SS recipients of C3SS kidneys. Graft survival was
significantly better when the donor organ possessed the C3F allotype (p<0.05).
Hazard ratio for graft loss of C3SS expressing kidney was 2.21 (95% CI: 1.04 to 4.72;
p=0.04). Graft function of C3FF/FS donor kidneys was significantly better than C3SS
donor kidneys (P<0.001). The effect of the C3F allotype was specific to this
combination of alleles. Multivariate analysis excluded an effect of other parameters
known to influence graft outcome
Analysis of the three-dimensional structure of C3 revealed, the glycine (C3F) to
arginine (C3S) amino acid change lies on the surface of the molecule. The amino
acids differ in size and charge, therefore may affect interactions with other proteins.
Expression of C3 alleles by donor renal cells can differentially affect late graft
outcome. Renal C3F allele expression in Caucasian C3SS recipients is associated with
a significantly better long-term outcome. These findings are consistent with possible
functional differences in the expressed donor C3F and C3S alleles.