Single Antigen Bead Cut-offs and their relationship with kidney graft survival

E.G. Kamburova, B.W. Wisse, A. van der Meer, I. Joosten, W.A. Allebes, L.B. Hilbrands, M.C. Baas, E. Spierings, C.E. Hack, F.E. van Reekum, A.D. van Zuilen, M.C. Verhaar, M.L. Bots, A.C.A.D. Drop, L. Plaisier, M.A.J. Seelen, J.S.F. Sanders, B. Hepkema, A.J. Lambeck, L.B. Bungener, C. Roozendaal, M.G.J. Tilanus, C.E.M. Voorter, L. Wieten, E.M. van Duijnhoven, M.A.C.J. Gelens, M.H.L. Christiaans, F.J. van Ittersum, A. Nurmohamed, N.M. Lardy, W. Swelsen, K.A.M.I. van der Pant, N.C. van der Weerd, I.J.M. ten Berge, F.J. Bemelman, A.J. Hoitsma, P.J.M. van der Boog, J.W. de Fijter, M.G.H. Betjes, S. Heidt, D.L. Roelen, F.H.J. Claas, H.G. Otten

Thursday 15 march 2018

15:30 - 15:35h at Willem Burger Foyer

Categories: Clinical, Session (poster)

Parallel session: Poster session 2: Clinical

Detection of HLA antibodies is commonly assessed by complement-dependent crossmatch testing and the much more sensitive Luminex technology. The presence of complement-fixing cytotoxic donor-specific HLA antibodies (DSA) prior to transplantation is considered a contraindication for transplantation. In the Dutch PROCARE Consortium study the impact of Luminex detected DSA on graft survival was determined for all crossmatch negative kidney transplantations performed between 1995 and 2006 for which pretransplant serum was available. The impact was most pronounced in the 3237 deceased-donor transplantations: transplantations positive for SAB detected DSA (N=430) had a 16% worse 10-year graft survival than those without DSA. In the assessment of bead positivity initially manufacturer instructions were followed.

There is no consensus however on the interpretation of single antigen bead measurements, on when to regard a bead positive for a specific antibody. To inform the debate, we studied the relationship between various beads positivity algorithms and the impact of resulting DSA positivity on graft survival. In a small three center comparison we first showed that the interassay variability can be greatly reduced and stabilised to an average absolute relative difference between 20% and 30%, when working with signal-to-background ratios instead of absolute fluorescence values. Next we compared the impact of a range of cut-off values for absolute MFI measurements, various signal-to-background ratios and combinations thereof on graft survival difference. We did not see a very strong impact of cut-off level on graft survival: DSA positive transplantations had a 14% poorer 10-year graft survival at an MFI cut-off of 500 (with 16% of transplants positive for DSA), increasing to 23% for a cut-off of 10,000 (with only 2% positive for DSA at that level). We only found a clear relationship between a cut-off level and deteriorating 1-year graft survival for DSA positive transplantations for the signal-to-background ratios, most pronounced with the lowest ranked antigen (LRA) taken as background. The signal-to-background ratios also resulted in the best 10-year graft survival discriminators, with highest graft survival difference of 25% for the DSA positive group, with 6% of the transplantations considered positive for DSA. With respect to risk stratification of graft survival, we therefore propose a signal-to-background ratio based on LRA with a cut-off level of 20.