Protective anti-donor IgM production after crossmatch positive liver-kidney transplantation

Abstract

The mechanism by which a liver transplantation might protect a simultaneous kidney transplant in a crossmatch-positive recipient is unknown. Flow cytometry crossmatch (FCXM) has increased the sensitivity of donor-specific antibody (DSA) detection compared with complement-dependant cytotoxicity (CDC). Here we compare the outcome of a liver-kidney transplantation (LKT), which was CDC and FCXM positive, to the mate-isolated kidney transplantation (KT), which was CDC negative but FCXM positive, from the same donor. Immunoglobulin G (IgG) and immunoglobulin M (IgM) DSAs were measured by FCXM using splenocytes and purified T cells. The KT graft was hyperacutely rejected and removed, but the LKT graft survived without episodes of rejection. Both the KT and the LKT recipients had high levels of circulating antidonor IgG, but not IgM, before transplantation. By day 3, antidonor IgG and IgM in the LKT recipient increased 2 and 7 fold respectively, whereas the KT recipient maintained the high IgG level but did not increase IgM. Histology of the KT graft showed IgG and complement (C1q) deposition, but in the LKT grafts, IgM was deposited without IgG or C1q. Circulating IgG and IgM DSAs returned to background by day 10 and were still at background on day 100. We report a crossmatch-positive LKT where posttransplantation production of IgM DSA, which failed to fix complement, appeared to protect the grafts.