Improved risk stratification of pretransplant donor specific antibodies with epitope analyses

E.G. Kamburova, B.W. Wisse, A. van der Meer, W.A. Allebes, I. Joosten, 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

12:25 - 12:35h at Willem Burger Zaal

Categories: Clinical, Session (parallel)

Parallel session: Parallel session 3: Clinical

The presence of (cytotoxic) antibodies against donor human leukocyte antigens (DSA) prior to transplantation is considered a contraindication for transplantation. Detection of these antibodies is widely used for donor exclusion. HLA antibody detection by single antigen bead assay (SAB) is much more sensitive than by complement-dependent crossmatches (CDC-XM). In the Dutch PROCARE Consortium study the impact of SAB detected DSA on graft survival was determined for all (CDC-XM 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. Due to the lack of a second field HLA typing of the donor, donor specificity of the SAB detected antibodies was initially determined at serological (split) level.

The SAB assay however allows for a second field definition of antibody specificity. On basis of the data present in the HLA epitope registry (http://www.epregistry.com.br) the most likely epitope specificity of the detected antibodies was defined. NMDP HLA-haplotype frequencies were used to determine the most likely second field HLA types of all recipients and donors in our cohort. Combination of these tools enabled the determination of donor anti-HLA-epitope specific antibodies (DESA) in the pretransplant serum. Pretransplant DESA positive deceased-donor transplantations (N=312) had a 20% poorer 10-year graft survival than those without DESA. A higher number of DESA led to an even worse graft survival i.e. transplantations with more than 2 DESA (N=236) had a 25% poorer graft survival compared to transplantations without DESA. We conclude that even without the exact knowledge of both the HLA-epitope specificity of the SAB detected antibodies and the mismatched donor HLA-epitopes, the number of pretransplant DESA might be a better parameter to stratify risk than the presence of serologically defined DSA.