Relevancy of cytokine autoantibodies in kidney transplantation

Serum concentrations of certain cytokines have been shown to be useful predictive biomarkers for graft outcome after kidney transplantation. Here we asked whether the biological effects of these cytokines on alloresponses could be modified by preformed autoantibodies. To answer this question, we have determined cytokine autoantibodies at the time of transplantation and compared their levels to histological manifestations of graft rejection.

We have developed a Luminex-based multiplex assay allowing the parallel measurement of autoantibodies against ten different cytokines (IFN-α, IFN-γ, IFN-ω, IL-6, IL-12, IL-17A, IL-17F, IL-22, TGF-β, GM-CSF) and the cell membrane protein Caveolin-1. Applying this technique, we evaluated the presence of these autoantibodies in the serum of 343 patients of whom 76 had available histological data from kidney transplant biopsies. Antibody levels were compared to the occurrence of acute and chronic graft rejection and other manifestations of graft damage during follow up.

The combination of different cytokine autoantibody values was able to accurately distinguish between different grades of graft damage according to the histological Banff classification.

Since the serum samples were taken prior to the respective transplantation, cytokine autoantibodies are promising tools for the determination of an individual inherent risk profile and potential therapeutic modifications. A follow-up study on the occurrence of cytokine autoantibodies during the post-transplantation period is ongoing.

This work was supported by the Volker-Homann-Foundation.