MOLECULAR ANALYSIS OF C3 ALLOTYPES RELATED TO TRANSPLANT OUTCOME IN HUMAN RENAL-ALLOGRAFTS

The third component of complement (C3) exists in two main allotypic fo rms, C3S and C3F, which can be distinguished at the molecular level us ing a variation of the polymerase chain reaction. An increased frequen cy of the C3F allele has been noted in a number of autoimmune and infl ammatory conditions affecting the kidney, including systemic vasculiti s, IgA nephropathy, and type II mesangiocapillary nephritis. Recently, in an unrelated study, we found (with small numbers) an increased inc idence of graft loss associated with the presence of the C3F allele. T o further assess this, we analyzed the S/F polymorphism in 183 donor-r ecipient pairs of patients undergoing renal transplantation. Forty-one of 183 grafts were lost, but graft loss was not associated with the C 3F allele over 14-month follow-up. However, the presence of the C3F al lele predicted an increased risk of graft dysfunction (defined as seru m creatinine >150 mu mol/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 all eles gave a relative risk for graft dysfunction of 1.8, suggesting a d ose-dependent effect, although numbers were small. The presence of the C3F allele was not significantly correlated with the number of reject ion episodes, serum creatinine, or duration of primary nonfunction. Th ese findings suggest that C3F may be a susceptibility allele for allog raft injury. Possible mechanisms for this association are discussed.