{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:43:37Z","timestamp":1792637017169,"version":"4.5.0"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"779","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n            Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)\u2013based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells. After transplant, the nonhuman primates maintained on 5C8-based immunosuppression had significantly better survival compared with those maintained on SOC immunosuppression (135.2 days versus 32.8 days,\n            <jats:italic>P<\/jats:italic>\n            = 0.013). The 5C8-treated group demonstrated better suppression of DSAs after transplant, more robust suppression of B cell populations, and better induction of regulatory T cells. Fewer infectious and welfare complications, including viral reactivation and weight loss, were also observed with 5C8-based immunosuppression compared with SOC immunosuppression. Therefore, anti-CD154 mAbs may improve kidney transplant outcomes through better control of posttransplant immune responses. The superior efficacy of anti-CD154 mAb\u2013based immunosuppression over tacrolimus-based SOC seen in this highly sensitized NHP transplant model suggests that anti-CD154 mAbs could potentially be used to desensitize and treat highly sensitized patients receiving kidney transplantation.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adn8130","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T18:58:41Z","timestamp":1735757921000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["CD154 blockade effectively controls antibody-mediated rejection in highly sensitized nonhuman primate kidney transplant recipients"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5075-4148","authenticated-orcid":true,"given":"Imran J.","family":"Anwar","sequence":"first","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-0918","authenticated-orcid":true,"given":"Isabel","family":"DeLaura","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-3725","authenticated-orcid":true,"given":"Joseph M.","family":"Ladowski","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9214-617X","authenticated-orcid":true,"given":"Davide","family":"Schilir\u00f2","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-7672","authenticated-orcid":true,"given":"Qimeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-6122","authenticated-orcid":true,"given":"Miriam","family":"Manook","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8543-194X","authenticated-orcid":true,"given":"Janghoon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0263-6738","authenticated-orcid":true,"given":"Rafaela","family":"Belloni","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7839-393X","authenticated-orcid":true,"given":"Angela","family":"Park","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1248-7269","authenticated-orcid":true,"given":"Daniel J.","family":"Schuster","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2462-9351","authenticated-orcid":true,"given":"Mingqing","family":"Song","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-1172","authenticated-orcid":true,"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics &amp; Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5534-7763","authenticated-orcid":true,"given":"Alton B.","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-2406","authenticated-orcid":true,"given":"Diogo","family":"Magnani","sequence":"additional","affiliation":[{"name":"Nonhuman Primate Reagent Resource, UMass Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyha","family":"Williams","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-5472","authenticated-orcid":true,"given":"Jean","family":"Kwun","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-385X","authenticated-orcid":true,"given":"Stuart J.","family":"Knechtle","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, 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