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Previous Volume 354:2014-2023 May 11, 2006 Number 19 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Soulillou, J.-P. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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.

Source Information

From the Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London (K.M.B., J.D.T., W.Z., S.H.S., N.S.S.); the Clinical Transplantation Laboratories, Guy's Hospital, London (E.K., R.W.V.); King's College Hospital, London (S.P.K.); Kent and Canterbury Hospital, Canterbury, United Kingdom (C.K.T.F.); the Department of Clinical Pharmacology, Barts and the London, Queen Mary's School of Medicine and Dentistry, London (X.H., A.J.); the Department of Histopathology, Guy's and St. Thomas' National Health Service Foundation Trust, London (C.H.); and the Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, the Netherlands (B.J.C.J., P.G.).

Address reprint requests to Dr. Sheerin at the Department of Nephrology and Transplantation, 5th Fl., Thomas Guy House, Guy's Hospital, London SE1 9RT, United Kingdom, or at neil.sheerin{at}kcl.ac.uk.

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