Impact of C3d-fixing donor-specific HLA antibodies on long-term kidney graft survival

E.G. Kamburova, B.W. Wisse, I. Joosten, W.A. Allebes, A. van der Meer, 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. Sanders, B.G Hepkema, A.J. Lambeck, L.B. Bungener, C. Roozendaal, M.G.J. Tilanus, C.E. Voorter, L. Wieten, E.M. van Duijnhoven, M.A.C.J. Gelens, M.H.L. Christiaans, F. van Ittersum, A. Nurmohamed, N.M. Lardy, W.T. 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

Chair(s): dr. M.H.L. Christiaans & dr. R.J. Toorop

Thursday 9 march 2017

8:00 - 8:12h at Johan de Meesterzaal

Categories: Parallel - Klinisch

Parallel session: Parallelsessie XI – Klinisch 3 - Early Bird sessie 2

The presence of complement fixing antibodies against donor human leukocyte antigens (HLA) prior to transplantation is considered a contraindication for transplantation. Detection of these antibodies by crossmatching is widely used in donor exclusion. HLA antibody detection by single antigen bead array (SAB) is much more sensitive than complement-dependent crossmatches and allows finer definition of antibody specificity. However, the exact clinical significance of SAB detected donor-specific antibodies (DSA) that do not cause a positive crossmatch is not clear. Although most studies showed a relation between SAB-defined DSA and impaired graft outcome, the presence of HLA antibodies in pre-or posttransplant sera not always resulted in graft loss. This raises the question how to define clinically relevant DSA using SAB, which is important as inclusion of irrelevant specificities in patients’ antibody profiles would result in dismissal of appropriate kidney donors. A recent modification of the pan-IgG SAB assay allows detection of HLA antibodies binding C1q and C3d. As early humoral graft rejection is considered to be complement mediated, these novel SAB-based techniques may provide a valuable tool in the identification of patients at risk for graft loss. C1q-fixing ability of DSA has already been shown to be strongly associated with kidney graft loss. Studies defining the potential of C3d as marker of complement fixation (e.g. assay developed by Immucor) are scarce and include low number sera from patients included up till now. In the Dutch PROCARE consortium study more than 6000 kidney transplantations performed between 1995-2006 were analyzed. The presence of non-donor-specific HLA antibodies (NDSA) and DSA against HLA-A/B/DR/DQ antigens was defined in 4724 pre-transplant sera using the pan-IgG SAB assay. Next, the 806 (17%) sera with DSA were further tested with the C3d-SAB assay. We found that 190/806 (24%) of the pretransplant sera contained at least one C3d-fixing DSA and 616/806 (76%) of the sera had no C3d-fixing DSA. At 10 years after transplantation, patients with C3d-fixing antibodies had a graft survival of 62%, while patients without C3d-fixing antibodies had a graft survival of 69%. Patients without any HLA antibodies had a 10-year graft survival of 79%. We conclude that the presence of pretransplant C3d-fixing DSA is associated with increased risk for graft rejection.