{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T17:13:11Z","timestamp":1771607591935,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The development of genetically modified pigs, which lack the expression of alpha 1\u20103 galactosyl transferase, (GalT\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre\u2010existing antibodies against the Gal epitope. However, antibodies against other antigens (anti\u2010non\u2010Gal antibodies), are found at varying levels in the pre\u2010transplant sera of most primates. We have previously found that baboons with high levels of pre\u2010transplant anti\u2010non\u2010Gal IgG, conditioned with a non\u2010myeloablative conditioning regimen, failed to engraft following pig\u2010to\u2010baboon bone marrow transplantation (Xenotransplantation, 17, 2010 and 300). Two baboons with low levels of pre\u2010transplant anti\u2010non\u2010Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28\u00a0days following transplantation, suggesting engraftment. These baboons also showed evidence of donor\u2010specific hyporesponsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre\u2010transplant anti\u2010non\u2010Gal IgG levels might improve engraftment levels following GalT\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> pig\u2010to\u2010baboon bone marrow transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five baboons, with low pre\u2010transplant anti\u2010non\u2010Gal IgG levels, received transplantation of bone marrow cells (1\u20135\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/kg of recipient weight) from GalT\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> pigs. They received a non\u2010myeloablative conditioning regimen consisting of low\u2010dose total body irradiation (TBI) (150\u00a0cGy), thymic irradiation (700\u00a0cGy), anti\u2010thymocyte globulin (<jats:styled-content style=\"fixed-case\">ATG<\/jats:styled-content>), and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra\u2010corporeal immunoadsorption using GalT\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> pig livers. Bone marrow engraftment was assessed by porcine\u2010specific <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> on colony forming units (<jats:styled-content style=\"fixed-case\">CFU<\/jats:styled-content>) of day 28 bone marrow aspirates. Anti\u2010non\u2010Gal antibody levels were assessed by serum binding toward GalT\u2010<jats:styled-content style=\"fixed-case\">KO PBMC<\/jats:styled-content> using flow cytometry (<jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content>). Peripheral macro\u2010chimerism was measured by <jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content> using pig and baboon\u2010specific antibodies and baboon anti\u2010pig cellular responses were assessed by mixed lymphocyte reactions (<jats:styled-content style=\"fixed-case\">MLR<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As previously reported, two of five baboons demonstrated detectable bone marrow engraftment at 4\u00a0weeks after transplantation. Engraftment was associated with lack of an increase in anti\u2010non\u2010Gal IgG levels as well as cellular hyporesponsiveness toward pig. Three subsequent baboons with similarly low levels of pre\u2010existing anti\u2010non\u2010Gal IgG showed no engraftment and an increase in anti\u2010non\u2010Gal IgG antibody levels following transplantation. Peripheral macrochimerism was only seen for a few days following transplantation regardless of antibody development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Selecting for baboon recipients with low levels of pre\u2010transplant anti\u2010non\u2010Gal IgG did not ensure bone marrow engraftment. Failure to engraft was associated with an increase in anti\u2010non\u2010Gal IgG levels following transplantation. These results suggest that anti\u2010non\u2010Gal\u2010IgG is likely involved in early bone marrow rejection and that successful strategies for combating anti\u2010non\u2010Gal IgG development may allow better engraftment. Since engraftment was only low and transient regardless of antibody development, innate immune, or species compatibility mechanisms will likely also need to be addressed to achieve long term engraftment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12065","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T06:46:36Z","timestamp":1383029196000},"page":"458-468","source":"Crossref","is-referenced-by-count":20,"title":["Increased levels of anti\u2010non\u2010Gal IgG following pig\u2010to\u2010baboon bone marrow transplantation correlate with failure of engraftment"],"prefix":"10.1111","volume":"20","author":[{"given":"Fan","family":"Liang","sequence":"first","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Wamala","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Scalea","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aseda","family":"Tena","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"Cormack","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon","family":"Pratts","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimon","family":"Duran\u2010Struuck","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahel","family":"Elias","sequence":"additional","affiliation":[{"name":"Transplant Unit Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hertl","sequence":"additional","affiliation":[{"name":"Transplant Unit Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christene A.","family":"Huang","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Sachs","sequence":"additional","affiliation":[{"name":"Transplantation Biology Research Center Department of Surgery Massachusetts General Hospital and Harvard Medical School Boston MA 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