Uric acid increases cellular and humoral alloimmunity in primary human peripheral blood mononuclear cells

Aim Hyperuricaemia is common among kidney transplant recipients and has been associated with worse graft outcome. Since episodes of acute cellular rejection and chronic humoral rejection contribute to decreased graft survival, in this study the effect of uric acid on cellular and humoral alloimmunity was evaluated. Methods Cellular alloimmunity was assessed by cell proliferation in two‐way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method in which humoral alloimmunity was induced in one‐way MLR. Then the de novo production of alloantibodies was measured with an antibody‐mediated complement‐dependent cytotoxicity assay, in which supernatants from the above MRLs were used against resting PBMC similar to the stimulator cells of the above MLRs. Results Uric acid at a concentration above its crystallization threshold increased cellular proliferation in two‐way MLRs. Supernatants from one‐way MLRs performed in the presence of uric acid were more cytotoxic against PBMC from individuals that had conferred the stimulator cells for the above MLRs. Conclusions Uric acid increases both cellular and humoral alloimmunity in human PBMC. These results offer a possible pathogenetic mechanism for the observed relation between hyperuricaemia and worse kidney allograft survival. Summary at a Glance Hyperuricemia is common among kidney transplant recipients and has been associated with worse graft outcome. The pathogenic mechanism of serum uric acid might be explained by the increasing of both cellular and humoral alloimmunity in human PBMC.