Affiliation:
1. Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital/Harvard Medical School Boston Massachusetts USA
2. Department of Pathology Massachusetts General Hospital/Harvard Medical School Boston Massachusetts USA
3. Revivicor Blacksburg Virginia USA
4. Tonix Pharmaceuticals Chatham New Jersey USA
5. Department of Transplantation Aichi Medical University Nagakute Japan
Abstract
AbstractAntibody‐mediated rejection (AMR) is a common cause of graft failure after pig‐to‐nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti‐CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti‐CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute‐onset AMR. The association of a urinary infection with graft rejection has been well‐documented in ABO‐incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.