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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\u2010CD154 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\u2010CD154 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\u2010onset AMR. The association of a urinary infection with graft rejection has been well\u2010documented in ABO\u2010incompatible 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.<\/jats:p>","DOI":"10.1111\/xen.12859","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T09:49:56Z","timestamp":1713779396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Novel factors potentially initiating acute antibody\u2010mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3267-906X","authenticated-orcid":false,"given":"Kohei","family":"Kinoshita","sequence":"first","affiliation":[{"name":"Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-4890","authenticated-orcid":false,"given":"Akihiro","family":"Maenaka","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-3202","authenticated-orcid":false,"given":"Ivy A.","family":"Rosales","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1360-938X","authenticated-orcid":false,"given":"Ahmad","family":"Karadagi","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8715-9134","authenticated-orcid":false,"given":"Toshihide","family":"Tomosugi","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[{"name":"Revivicor  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-1455","authenticated-orcid":false,"given":"Seth","family":"Lederman","sequence":"additional","affiliation":[{"name":"Tonix Pharmaceuticals  Chatham New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-4150","authenticated-orcid":false,"given":"Robert B.","family":"Colvin","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-4603","authenticated-orcid":false,"given":"Tatsuo","family":"Kawai","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3764-4590","authenticated-orcid":false,"suffix":"III","given":"Richard N.","family":"Pierson","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital\/Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8335-0361","authenticated-orcid":false,"given":"Takaaki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Transplantation Aichi Medical University  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8899-9431","authenticated-orcid":false,"given":"David K. 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