Donor Cytokine Genotype Influences the Development of Acute Rejection After Renal Transplantation

Abstract

This study identifies donor IL-6 genotype as a major genetic risk factor for the development of acute rejection after renal transplantation. This provides evidence that donor-derived cytokines play a major role in determining outcome after transplantation, and will contribute to the development of therapeutic algorithms to predict individuals at particularly high risk of acute rejection.

Impact of donor and recipient cytokine genotypes on renal allograft outcome

“…This effect was independent of other major genetic determinants of AR, even donor-recipient HLA-DR matching. 5 In our study the probed population was selected with full HLA-DR matching and we could not see the described association, but we did find a significant correlation between donor IL-6 Ϫ174 CC genotype and CR injured grafts. This genotype remains a strong donor factor predictive of allograft outcome.…”

“…IL-6, a pleotropic cytokine mediator of the acute phase response, was reported in another study 5 as an impact factor predictive of the incidence and severity of AR after renal transplantation when donor genotype was IL-6 Ϫ174 CC. This effect was independent of other major genetic determinants of AR, even donor-recipient HLA-DR matching.…”

“…Like in other studies, we did observe associations between clinical outcome and gene variants. 2,5,9 Nevertheless, these were not clear enough to identify high-risk patients or direct immunosuppressive regimens. To elucidate the consequences of gene variants in allograft immunological outcomes, further efforts must be made to increase sample size and include a multivariate analysis in the statistical study.…”

“…4,5 Genomic DNA was extracted from frozen buffy coats or spleen cells of cadaver donors using a "salting-out" procedure.…”

The Possible Protective Role of the Il6-174GC Genotype in Dengue Fever

“…Some of these polymorphisms seem to be correlated to its production [18][19][20][21][22][23][24][25], and potentially conferring flexibility to immune response. The presence of certain genotypes may influence the course of both viral and bacterial infections [13,[26][27][28][29], as well as be associated to susceptibility or resistance to auto-immune diseases [30,31], or influence both solid organ post-transplant rejection processes [32,33], and graft versus host disease post bone-marrow transplantation [34,35].…”