Impaired kidney graft survival is associated with the TNF-alpha genotype

The TNF2 allele at position -308 of the tumor necrosis factor (TNF)-alpha gene is associated with high TNF production. The purpose was to study the association of this gene polymorphism with rejection episodes and graft survival after kidney transplantation.

A retrospective analysis of transplant outcomes of patients who only had been treated with one single form of immunosuppression consisting of cyclosporine, azathioprine, and prednisolon was performed.

We found that 115 (73%) patients had the TNF1/TNF1 genotype, whereas 42 (27%) were TNF2 positive. There was no difference in the overall acute rejection frequency between these two groups (50% in each), but our data showed a non-significant tendency towards a higher frequency of steroid resistant rejections in the TNF2 positive group (57% vs. 40%). There was no significant difference in graft survival between the two genotype groups, although an early tendency towards worse survival was seen in TNF2 recipients. However, the TNF2 positive recipients with rejection episodes had far worse graft survival compared with the TNF1/TNF1 recipients with rejection episodes (P<0.02). No difference was seen between the two genotype groups in patients without rejection episodes.

Our data propose that potentially high TNF producers with the TNF2 allele do not have an increased risk for rejection episodes, but if rejection episodes occur, they have a significantly increased risk for early graft loss. TNF production may intensify rejection, but is not a primary factor for the induction of such acute immune activation.