Xenotransplantation of Galactosyl-Transferase Knockout, CD55, CD59, CD39, and Fucosyl-Transferase Transgenic Pig Kidneys Into Baboons
Identifieur interne : 001473 ( PascalFrancis/Checkpoint ); précédent : 001472; suivant : 001474Xenotransplantation of Galactosyl-Transferase Knockout, CD55, CD59, CD39, and Fucosyl-Transferase Transgenic Pig Kidneys Into Baboons
Auteurs : S. Le Bas-Bernardet [France] ; X. Tillou [France] ; N. Poirier [France] ; N. Dilek [France] ; M. Chatelais [France] ; J. Devalliere [France] ; B. Charreau [France] ; D. Minault [France] ; J. Hervouet [France] ; K. Renaudin [France] ; C. Crossan [Royaume-Uni] ; L. Scobie [Royaume-Uni] ; P. J. Cowan [Australie] ; A. J. F. D'Apice [Australie] ; C. Galli [Italie] ; E. Cozzi [Italie] ; J. P. Soulillou [France] ; B. Vanhove [France] ; G. Blancho [France]Source :
- Transplantation proceedings [ 0041-1345 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Animal transgénique, Singe, Médecine.
English descriptors
- KwdEn :
Abstract
Galactosyl-transferase knockout (GT-KO) pigs represent the latest major progress to reduce immune reactions in xenotransplantation. However, their organs are still subject to rapid humoral rejection involving complement activation requiring the ongoing development of further genetic modifications in the pig. In a pig-to-baboon renal transplantation setting, we have used donor pigs that are not only GT-KO, but also transgenic for human CD55 (hCD55), hCD59, hCD39, and fucosyl-transferase (hHT). We studied kidney xenograft survival, physiological and immunologic parameters, xenogeneic rejection characteristics, as well as viral transmission aspects among two groups of baboons: control animals (n = 2), versus those (n = 4) treated with a cocktail of cyclophosphamide, tacrolimus, mycophenolate mofetil, steroids, and a recombinant human C1 inhibitor. Whereas control animals showed clear acute humoral rejection at around day 4, the treated animals showed moderately improved graft survival with rejection at around 2 weeks posttransplantation. Biopsies showed signs of acute vascular rejection (interstitial hemorrhage, glomerular thrombi, and acute tubular necrosis) as well as immunoglobulin (Ig)M and complement deposition in the glomerular and peritubular capillaries. The low level of preformed non-Gal-α1.3Gal IgM detected prior to transplantation increased at 6 days posttransplantation, whereas induced IgG appeared after day 6. No porcine endogenous retrovirus (PERV) transmission was detected in any transplanted baboon. Thus, surprisingly, organs from the GT-KO, hCD55, hCD59, hCD39, and hHT transgenic donors did not appear to convey significant protection against baboon anti-pig antibodies and complement activation, which obviously continue to be significant factors under a suboptimal immunosuppression regimen. The association, timing, and doses of immunosuppressive drugs remain critical. They will have to be optimized to achieve longer graft survivals.
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Charreau</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Minault, D" sort="Minault, D" uniqKey="Minault D" first="D." last="Minault">D. Minault</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Hervouet, J" sort="Hervouet, J" uniqKey="Hervouet J" first="J." last="Hervouet">J. Hervouet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Renaudin, K" sort="Renaudin, K" uniqKey="Renaudin K" first="K." last="Renaudin">K. Renaudin</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Pathology Laboratory, CHU-Hôtel Dieu</s1><s2>Nantes</s2><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Crossan, C" sort="Crossan, C" uniqKey="Crossan C" first="C." last="Crossan">C. Crossan</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1><s2>Glasgow</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Scobie, L" sort="Scobie, L" uniqKey="Scobie L" first="L." last="Scobie">L. Scobie</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1><s2>Glasgow</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Cowan, P J" sort="Cowan, P J" uniqKey="Cowan P" first="P. J." last="Cowan">P. J. Cowan</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1><s2>Victoria</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="D Apice, A J F" sort="D Apice, A J F" uniqKey="D Apice A" first="A. J. F." last="D'Apice">A. J. F. D'Apice</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1><s2>Victoria</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Galli, C" sort="Galli, C" uniqKey="Galli C" first="C." last="Galli">C. Galli</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>The Laboratorio di Tecnologie della Riproduzione, LTR</s1><s2>Cremona</s2><s3>ITA</s3><sZ>15 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Cremona</wicri:noRegion></affiliation></author><author><name sortKey="Cozzi, E" sort="Cozzi, E" uniqKey="Cozzi E" first="E." last="Cozzi">E. Cozzi</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Consorzio per la Ricerca sul Trapianto d'Organi, CORIT</s1><s2>Padua</s2><s3>ITA</s3><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Padua</wicri:noRegion></affiliation></author><author><name sortKey="Soulillou, J P" sort="Soulillou, J P" uniqKey="Soulillou J" first="J. P." last="Soulillou">J. P. Soulillou</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Vanhove, B" sort="Vanhove, B" uniqKey="Vanhove B" first="B." last="Vanhove">B. Vanhove</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Blancho, G" sort="Blancho, G" uniqKey="Blancho G" first="G." last="Blancho">G. Blancho</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0017503</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 12-0017503 INIST</idno><idno type="RBID">Pascal:12-0017503</idno><idno type="wicri:Area/PascalFrancis/Corpus">001737</idno><idno type="wicri:Area/PascalFrancis/Curation">004772</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">001473</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">001473</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Xenotransplantation of Galactosyl-Transferase Knockout, CD55, CD59, CD39, and Fucosyl-Transferase Transgenic Pig Kidneys Into Baboons</title><author><name sortKey="Le Bas Bernardet, S" sort="Le Bas Bernardet, S" uniqKey="Le Bas Bernardet S" first="S." last="Le Bas-Bernardet">S. Le Bas-Bernardet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Tillou, X" sort="Tillou, X" uniqKey="Tillou X" first="X." last="Tillou">X. Tillou</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Poirier, N" sort="Poirier, N" uniqKey="Poirier N" first="N." last="Poirier">N. Poirier</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Dilek, N" sort="Dilek, N" uniqKey="Dilek N" first="N." last="Dilek">N. Dilek</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Chatelais, M" sort="Chatelais, M" uniqKey="Chatelais M" first="M." last="Chatelais">M. Chatelais</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Devalliere, J" sort="Devalliere, J" uniqKey="Devalliere J" first="J." last="Devalliere">J. Devalliere</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Charreau, B" sort="Charreau, B" uniqKey="Charreau B" first="B." last="Charreau">B. Charreau</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Minault, D" sort="Minault, D" uniqKey="Minault D" first="D." last="Minault">D. Minault</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Hervouet, J" sort="Hervouet, J" uniqKey="Hervouet J" first="J." last="Hervouet">J. Hervouet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Renaudin, K" sort="Renaudin, K" uniqKey="Renaudin K" first="K." last="Renaudin">K. Renaudin</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Pathology Laboratory, CHU-Hôtel Dieu</s1><s2>Nantes</s2><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Crossan, C" sort="Crossan, C" uniqKey="Crossan C" first="C." last="Crossan">C. Crossan</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1><s2>Glasgow</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Scobie, L" sort="Scobie, L" uniqKey="Scobie L" first="L." last="Scobie">L. Scobie</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1><s2>Glasgow</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Cowan, P J" sort="Cowan, P J" uniqKey="Cowan P" first="P. J." last="Cowan">P. J. Cowan</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1><s2>Victoria</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="D Apice, A J F" sort="D Apice, A J F" uniqKey="D Apice A" first="A. J. F." last="D'Apice">A. J. F. D'Apice</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1><s2>Victoria</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Galli, C" sort="Galli, C" uniqKey="Galli C" first="C." last="Galli">C. Galli</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>The Laboratorio di Tecnologie della Riproduzione, LTR</s1><s2>Cremona</s2><s3>ITA</s3><sZ>15 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Cremona</wicri:noRegion></affiliation></author><author><name sortKey="Cozzi, E" sort="Cozzi, E" uniqKey="Cozzi E" first="E." last="Cozzi">E. Cozzi</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Consorzio per la Ricerca sul Trapianto d'Organi, CORIT</s1><s2>Padua</s2><s3>ITA</s3><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Padua</wicri:noRegion></affiliation></author><author><name sortKey="Soulillou, J P" sort="Soulillou, J P" uniqKey="Soulillou J" first="J. P." last="Soulillou">J. P. Soulillou</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Vanhove, B" sort="Vanhove, B" uniqKey="Vanhove B" first="B." last="Vanhove">B. Vanhove</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Blancho, G" sort="Blancho, G" uniqKey="Blancho G" first="G." last="Blancho">G. Blancho</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Transplantation proceedings</title><title level="j" type="abbreviated">Transplant. proc.</title><idno type="ISSN">0041-1345</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Transplantation proceedings</title><title level="j" type="abbreviated">Transplant. proc.</title><idno type="ISSN">0041-1345</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Baboon</term><term>Decay accelerating factor</term><term>Gene</term><term>Graft</term><term>Heterotransplantation</term><term>Kidney</term><term>Medicine</term><term>Monkey</term><term>Mutation</term><term>Pig</term><term>Primates</term><term>Transferases</term><term>Transgenic animal</term><term>Transplantation</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Hétérotransplantation</term><term>Transferases</term><term>Gène</term><term>Mutation</term><term>Facteur accélérateur dissociation</term><term>Animal transgénique</term><term>Porc</term><term>Rein</term><term>Primates</term><term>Singe</term><term>Médecine</term><term>Transplantation</term><term>Greffe</term><term>Traitement</term><term>Antigène CD55</term><term>Antigène CD59</term><term>Antigène CD39</term><term>Babouin</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Animal transgénique</term><term>Singe</term><term>Médecine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Galactosyl-transferase knockout (GT-KO) pigs represent the latest major progress to reduce immune reactions in xenotransplantation. However, their organs are still subject to rapid humoral rejection involving complement activation requiring the ongoing development of further genetic modifications in the pig. In a pig-to-baboon renal transplantation setting, we have used donor pigs that are not only GT-KO, but also transgenic for human CD55 (hCD55), hCD59, hCD39, and fucosyl-transferase (hHT). We studied kidney xenograft survival, physiological and immunologic parameters, xenogeneic rejection characteristics, as well as viral transmission aspects among two groups of baboons: control animals (n = 2), versus those (n = 4) treated with a cocktail of cyclophosphamide, tacrolimus, mycophenolate mofetil, steroids, and a recombinant human C1 inhibitor. Whereas control animals showed clear acute humoral rejection at around day 4, the treated animals showed moderately improved graft survival with rejection at around 2 weeks posttransplantation. Biopsies showed signs of acute vascular rejection (interstitial hemorrhage, glomerular thrombi, and acute tubular necrosis) as well as immunoglobulin (Ig)M and complement deposition in the glomerular and peritubular capillaries. The low level of preformed non-Gal-α1.3Gal IgM detected prior to transplantation increased at 6 days posttransplantation, whereas induced IgG appeared after day 6. No porcine endogenous retrovirus (PERV) transmission was detected in any transplanted baboon. Thus, surprisingly, organs from the GT-KO, hCD55, hCD59, hCD39, and hHT transgenic donors did not appear to convey significant protection against baboon anti-pig antibodies and complement activation, which obviously continue to be significant factors under a suboptimal immunosuppression regimen. The association, timing, and doses of immunosuppressive drugs remain critical. They will have to be optimized to achieve longer graft survivals.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0041-1345</s0></fA01><fA02 i1="01"><s0>TRPPA8</s0></fA02><fA03 i2="1"><s0>Transplant. proc.</s0></fA03><fA05><s2>43</s2></fA05><fA06><s2>9</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Xenotransplantation of Galactosyl-Transferase Knockout, CD55, CD59, CD39, and Fucosyl-Transferase Transgenic Pig Kidneys Into Baboons</s1></fA08><fA11 i1="01" i2="1"><s1>LE BAS-BERNARDET (S.)</s1></fA11><fA11 i1="02" i2="1"><s1>TILLOU (X.)</s1></fA11><fA11 i1="03" i2="1"><s1>POIRIER (N.)</s1></fA11><fA11 i1="04" i2="1"><s1>DILEK (N.)</s1></fA11><fA11 i1="05" i2="1"><s1>CHATELAIS (M.)</s1></fA11><fA11 i1="06" i2="1"><s1>DEVALLIERE (J.)</s1></fA11><fA11 i1="07" i2="1"><s1>CHARREAU (B.)</s1></fA11><fA11 i1="08" i2="1"><s1>MINAULT (D.)</s1></fA11><fA11 i1="09" i2="1"><s1>HERVOUET (J.)</s1></fA11><fA11 i1="10" i2="1"><s1>RENAUDIN (K.)</s1></fA11><fA11 i1="11" i2="1"><s1>CROSSAN (C.)</s1></fA11><fA11 i1="12" i2="1"><s1>SCOBIE (L.)</s1></fA11><fA11 i1="13" i2="1"><s1>COWAN (P. J.)</s1></fA11><fA11 i1="14" i2="1"><s1>D'APICE (A. J. F.)</s1></fA11><fA11 i1="15" i2="1"><s1>GALLI (C.)</s1></fA11><fA11 i1="16" i2="1"><s1>COZZI (E.)</s1></fA11><fA11 i1="17" i2="1"><s1>SOULILLOU (J. P.)</s1></fA11><fA11 i1="18" i2="1"><s1>VANHOVE (B.)</s1></fA11><fA11 i1="19" i2="1"><s1>BLANCHO (G.)</s1></fA11><fA14 i1="01"><s1>Institut de Transplantation-Urologie-Néphrologie, ITUN and INSERM UMR643</s1><s2>Nantes</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></fA14><fA14 i1="02"><s1>Pathology Laboratory, CHU-Hôtel Dieu</s1><s2>Nantes</s2><s3>FRA</s3><sZ>10 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Biological and Biomedical Sciences, Glasgow Caledonian University</s1><s2>Glasgow</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="04"><s1>Immunology Research Centre, St Vicent's Hospital</s1><s2>Victoria</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>14 aut.</sZ></fA14><fA14 i1="05"><s1>The Laboratorio di Tecnologie della Riproduzione, LTR</s1><s2>Cremona</s2><s3>ITA</s3><sZ>15 aut.</sZ></fA14><fA14 i1="06"><s1>Consorzio per la Ricerca sul Trapianto d'Organi, CORIT</s1><s2>Padua</s2><s3>ITA</s3><sZ>16 aut.</sZ></fA14><fA20><s1>3426-3430</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>14765</s2><s5>354000507348890670</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>14 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0017503</s0></fA47><fA60><s1>P</s1><s2>C</s2></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Transplantation proceedings</s0></fA64><fA66 i1="01"><s0>NLD</s0></fA66><fC01 i1="01" l="ENG"><s0>Galactosyl-transferase knockout (GT-KO) pigs represent the latest major progress to reduce immune reactions in xenotransplantation. However, their organs are still subject to rapid humoral rejection involving complement activation requiring the ongoing development of further genetic modifications in the pig. In a pig-to-baboon renal transplantation setting, we have used donor pigs that are not only GT-KO, but also transgenic for human CD55 (hCD55), hCD59, hCD39, and fucosyl-transferase (hHT). We studied kidney xenograft survival, physiological and immunologic parameters, xenogeneic rejection characteristics, as well as viral transmission aspects among two groups of baboons: control animals (n = 2), versus those (n = 4) treated with a cocktail of cyclophosphamide, tacrolimus, mycophenolate mofetil, steroids, and a recombinant human C1 inhibitor. Whereas control animals showed clear acute humoral rejection at around day 4, the treated animals showed moderately improved graft survival with rejection at around 2 weeks posttransplantation. Biopsies showed signs of acute vascular rejection (interstitial hemorrhage, glomerular thrombi, and acute tubular necrosis) as well as immunoglobulin (Ig)M and complement deposition in the glomerular and peritubular capillaries. The low level of preformed non-Gal-α1.3Gal IgM detected prior to transplantation increased at 6 days posttransplantation, whereas induced IgG appeared after day 6. No porcine endogenous retrovirus (PERV) transmission was detected in any transplanted baboon. Thus, surprisingly, organs from the GT-KO, hCD55, hCD59, hCD39, and hHT transgenic donors did not appear to convey significant protection against baboon anti-pig antibodies and complement activation, which obviously continue to be significant factors under a suboptimal immunosuppression regimen. The association, timing, and doses of immunosuppressive drugs remain critical. They will have to be optimized to achieve longer graft survivals.</s0></fC01><fC02 i1="01" i2="X"><s0>002B25</s0></fC02><fC02 i1="02" i2="X"><s0>002A06F</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Hétérotransplantation</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Heterotransplantation</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Heterotrasplante</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Transferases</s0><s2>FE</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Transferases</s0><s2>FE</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Transferases</s0><s2>FE</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Gène</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Gene</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Gen</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Mutation</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Mutation</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" 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l="ENG"><s0>Primates</s0><s2>NS</s2><s5>12</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Primates</s0><s2>NS</s2><s5>12</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Singe</s0><s5>17</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Monkey</s0><s5>17</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Mono</s0><s5>17</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Médecine</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Medicine</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Medicina</s0><s5>18</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Transplantation</s0><s5>19</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Transplantation</s0><s5>19</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Trasplantación</s0><s5>19</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Greffe</s0><s5>25</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Graft</s0><s5>25</s5></fC03><fC03 i1="13" i2="X" l="SPA"><s0>Injerto</s0><s5>25</s5></fC03><fC03 i1="14" i2="X" l="FRE"><s0>Traitement</s0><s5>26</s5></fC03><fC03 i1="14" i2="X" l="ENG"><s0>Treatment</s0><s5>26</s5></fC03><fC03 i1="14" i2="X" l="SPA"><s0>Tratamiento</s0><s5>26</s5></fC03><fC03 i1="15" i2="X" l="FRE"><s0>Antigène CD55</s0><s4>INC</s4><s5>86</s5></fC03><fC03 i1="16" i2="X" l="FRE"><s0>Antigène CD59</s0><s4>INC</s4><s5>87</s5></fC03><fC03 i1="17" i2="X" l="FRE"><s0>Antigène CD39</s0><s4>INC</s4><s5>88</s5></fC03><fC03 i1="18" i2="X" l="FRE"><s0>Babouin</s0><s4>CD</s4><s5>96</s5></fC03><fC03 i1="18" i2="X" l="ENG"><s0>Baboon</s0><s4>CD</s4><s5>96</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Artiodactyla</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Artiodactyla</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Artiodactyla</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Ungulata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Ungulata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Ungulata</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Chirurgie</s0><s5>37</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Surgery</s0><s5>37</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Cirugía</s0><s5>37</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Génétique</s0><s5>38</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Genetics</s0><s5>38</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Genética</s0><s5>38</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Appareil urinaire</s0><s5>39</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Urinary system</s0><s5>39</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Aparato urinario</s0><s5>39</s5></fC07><fN21><s1>002</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA><pR><fA30 i1="01" i2="1" l="ENG"><s1>The French Speaking Society of Transplantation and Transplantation Sans Frontières. Congrès</s1><s3>Geneva CHE</s3><s4>2000-12-15</s4></fA30></pR></standard></inist><affiliations><list><country><li>Australie</li><li>France</li><li>Italie</li><li>Royaume-Uni</li></country><region><li>Pays de la Loire</li></region><settlement><li>Nantes</li></settlement></list><tree><country name="France"><region name="Pays de la Loire"><name sortKey="Le Bas Bernardet, S" sort="Le Bas Bernardet, S" uniqKey="Le Bas Bernardet S" first="S." last="Le Bas-Bernardet">S. Le Bas-Bernardet</name></region><name sortKey="Blancho, G" sort="Blancho, G" uniqKey="Blancho G" first="G." last="Blancho">G. Blancho</name><name sortKey="Charreau, B" sort="Charreau, B" uniqKey="Charreau B" first="B." last="Charreau">B. Charreau</name><name sortKey="Chatelais, M" sort="Chatelais, M" uniqKey="Chatelais M" first="M." last="Chatelais">M. Chatelais</name><name sortKey="Devalliere, J" sort="Devalliere, J" uniqKey="Devalliere J" first="J." last="Devalliere">J. Devalliere</name><name sortKey="Dilek, N" sort="Dilek, N" uniqKey="Dilek N" first="N." last="Dilek">N. Dilek</name><name sortKey="Hervouet, J" sort="Hervouet, J" uniqKey="Hervouet J" first="J." last="Hervouet">J. Hervouet</name><name sortKey="Minault, D" sort="Minault, D" uniqKey="Minault D" first="D." last="Minault">D. Minault</name><name sortKey="Poirier, N" sort="Poirier, N" uniqKey="Poirier N" first="N." last="Poirier">N. Poirier</name><name sortKey="Renaudin, K" sort="Renaudin, K" uniqKey="Renaudin K" first="K." last="Renaudin">K. Renaudin</name><name sortKey="Soulillou, J P" sort="Soulillou, J P" uniqKey="Soulillou J" first="J. P." last="Soulillou">J. P. Soulillou</name><name sortKey="Tillou, X" sort="Tillou, X" uniqKey="Tillou X" first="X." last="Tillou">X. Tillou</name><name sortKey="Vanhove, B" sort="Vanhove, B" uniqKey="Vanhove B" first="B." last="Vanhove">B. Vanhove</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Crossan, C" sort="Crossan, C" uniqKey="Crossan C" first="C." last="Crossan">C. Crossan</name></noRegion><name sortKey="Scobie, L" sort="Scobie, L" uniqKey="Scobie L" first="L." last="Scobie">L. Scobie</name></country><country name="Australie"><noRegion><name sortKey="Cowan, P J" sort="Cowan, P J" uniqKey="Cowan P" first="P. J." last="Cowan">P. J. Cowan</name></noRegion><name sortKey="D Apice, A J F" sort="D Apice, A J F" uniqKey="D Apice A" first="A. J. F." last="D'Apice">A. J. F. D'Apice</name></country><country name="Italie"><noRegion><name sortKey="Galli, C" sort="Galli, C" uniqKey="Galli C" first="C." last="Galli">C. Galli</name></noRegion><name sortKey="Cozzi, E" sort="Cozzi, E" uniqKey="Cozzi E" first="E." last="Cozzi">E. Cozzi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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