Klinisch II - P25 - Identification of non-HLA antibody targets in kidney trans­plan­tation for a new diagnostic assay

L.A. Michielsen, H.G. Otten, M.M. Krebber, A.D van Zuilen, M.C. Verhaar

Chair(s): drs. Christina Krikke, chirurg, UMC Groningen

Thursday 10 march 2016

13:00 - 13:30h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

HLA antibodies are an established risk factor for antibody-mediated rejection and impaired graft survival. Evidence originating from HLA identical sibling transplants indicates that non-HLA antibodies play a role as well. Numerous non-HLA antibodies directed against a heterogeneous subset of both allow- and autoantigens have been identified in renal transplantation. Standardized assays for the measurement of non-HLA antibodies are lacking. We performed a literature study to determine which non-HLA antibody targets should be implemented in a new assay. 

In 106 studies over 3000 potential non-HLA antigens were described in renal transplant patients, and antibodies against 21 of these were found to be associated with a poor prognosis such as autoantibodies directed against recently discovered targets including agrin and endorepellin. The most extensively studied non-HLA antibodies were MHC class I related chain A antibodies, anti-endothelial cell antibodies and anti-angiotensin II type 1 receptor antibodies. In addition, multiple groups also studied endothelin-1 type A receptor and vimentin antibodies. 

Several studies have indicated that the presence of non-HLA antibodies is a risk indicator for rejection and decreased graft survival. However, assembling of these results in order to determine the exact clinical relevance is limited by heterogenic study populations and outcome measures, and also by different testing methods and large variations in reported incidences of antibodies even with the same assay. 

The exact clinical relevance of non-HLA antibodies has yet to be determined because of highly heterogenic study designs and inconclusive results in a number of studies. However, it is hypothesized that non-HLA antibodies are associated with impaired graft outcome and that non-HLA and HLA-antibodies have a synergistic effect. HLA antibodies can evoke endothelial damage and subsequent exposure to selfantigens, amplifies inflammation caused by binding of non-HLA antibodies activating complement. Considering the number of newly identified non-HLA antibodies and technical difficulties with current assays, the development of a new diagnostic assay is warranted. Preferentially, this assay would measure multiple antibodies at once as this will provide valuable information regarding the role of non-HLA antibodies in rejection and could eventually help identifying different risk profiles for rejection and impaired graft survival.