Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates
Background We aimed to investigate (a) the long‐term survival of corneal grafts from α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pigs in non‐human primates as a primary outcome and (b) the effect of anti‐CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary ou...
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| Veröffentlicht in: | Xenotransplantation (Københaven) 2020-01, Vol.27 (1), p.e12559-n/a |
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| container_title | Xenotransplantation (Københaven) |
| container_volume | 27 |
| creator | Yoon, Chang Ho Choi, Se Hyun Choi, Hyuk Jin Lee, Hyun Ju Kang, Hee Jung Kim, Jong Min Park, Chung‐Gyu Choi, Kimyung Kim, Hyunil Ahn, Curie Kim, Mee Kum |
| description | Background
We aimed to investigate (a) the long‐term survival of corneal grafts from α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pigs in non‐human primates as a primary outcome and (b) the effect of anti‐CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome.
Methods
Nine rhesus macaques undergoing full‐thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti‐CD20 antibody.
Results
Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7‐ month‐old) and younger (≤7‐month‐old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti‐αGal IgG/M levels were unchanged in both groups. At last examination, anti‐non‐Gal IgG was increased in the control group alone (P = .013).
Conclusions
The GTKOm pig corneal graft achieved long‐term survival when combined with anti‐CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas. |
| doi_str_mv | 10.1111/xen.12559 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2299446360</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2351282441</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2689-425acf4a12190649af3ac8ef3b3990b427dc240c44fb9caaabe68487fe7b4c883</originalsourceid><addsrcrecordid>eNp10T1uFDEUB3ALgcgSKLgAskQDEpP4a7x2iaJAIq2gASndyOM8T5ydsRd7HNiOI9BwEC6SQ3CSONlAgYQbS34__W2_h9BzSg5oXYffIBxQ1rb6AVpQrnXDidIP0YJoohop27M99CTnS0IIb1X7GO1x2krJJF2gn6sYht_ff8yQJpxLuvJXZsTRYVfG8fb8wtt1gJyxjSlArdXL4pCMmzN2KU74-hd9w6sczGjsHPN2nJMJ2UEyGfAAAWpxHaJdxzLjyQdv5pIAb_yQsQ84xFDBRZlMwJvkJzNDfooeOTNmeHa_76PP744_HZ00q4_vT4_erhrLpNKNYK2xThjKqCZSaOO4sQoc72sTSC_Y8twyQawQrtfWGNODVEItHSx7YZXi--jVLneT4pcCee4mny2MowkQS-4Y01oIySWp9OU_9DKWFOrrOsZbyhQTglb1eqdsijkncN3dl9K2o6S7nVVX29fdzaraF_eJpZ_g_K_8M5wKDnfgqx9h-_-k7uz4wy7yBnqxpzE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2351282441</pqid></control><display><type>article</type><title>Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Yoon, Chang Ho ; Choi, Se Hyun ; Choi, Hyuk Jin ; Lee, Hyun Ju ; Kang, Hee Jung ; Kim, Jong Min ; Park, Chung‐Gyu ; Choi, Kimyung ; Kim, Hyunil ; Ahn, Curie ; Kim, Mee Kum</creator><creatorcontrib>Yoon, Chang Ho ; Choi, Se Hyun ; Choi, Hyuk Jin ; Lee, Hyun Ju ; Kang, Hee Jung ; Kim, Jong Min ; Park, Chung‐Gyu ; Choi, Kimyung ; Kim, Hyunil ; Ahn, Curie ; Kim, Mee Kum</creatorcontrib><description>Background
We aimed to investigate (a) the long‐term survival of corneal grafts from α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pigs in non‐human primates as a primary outcome and (b) the effect of anti‐CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome.
Methods
Nine rhesus macaques undergoing full‐thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti‐CD20 antibody.
Results
Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7‐ month‐old) and younger (≤7‐month‐old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti‐αGal IgG/M levels were unchanged in both groups. At last examination, anti‐non‐Gal IgG was increased in the control group alone (P = .013).
Conclusions
The GTKOm pig corneal graft achieved long‐term survival when combined with anti‐CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.</description><identifier>ISSN: 0908-665X</identifier><identifier>EISSN: 1399-3089</identifier><identifier>DOI: 10.1111/xen.12559</identifier><identifier>PMID: 31566261</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Animals ; Animals, Genetically Modified ; Antibodies, Monoclonal - therapeutic use ; Antigens, CD20 - immunology ; anti‐CD20 antibody ; B-Lymphocytes - physiology ; CD20 antigen ; complement ; Complement component C3a ; Cornea ; Corneal Transplantation ; Galactosyltransferases - genetics ; Gene Knockout Techniques ; Graft Rejection - prevention & control ; Graft Survival ; Heterografts - physiology ; Hogs ; Humans ; Immunoglobulin G ; Intravenous administration ; Lymphocyte Activation ; Lymphocytes B ; Monoclonal antibodies ; non‐Gal ; non‐human primate ; Primates ; Swine ; Swine, Miniature ; Tacrolimus ; Transplantation, Heterologous ; Xenografts ; xenotransplantation ; α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pig</subject><ispartof>Xenotransplantation (Københaven), 2020-01, Vol.27 (1), p.e12559-n/a</ispartof><rights>2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2689-425acf4a12190649af3ac8ef3b3990b427dc240c44fb9caaabe68487fe7b4c883</citedby><cites>FETCH-LOGICAL-c2689-425acf4a12190649af3ac8ef3b3990b427dc240c44fb9caaabe68487fe7b4c883</cites><orcidid>0000-0003-1249-6181 ; 0000-0001-7033-1102 ; 0000-0001-7022-4331 ; 0000-0003-2203-5709 ; 0000-0001-9313-1322 ; 0000-0002-7314-2267 ; 0000-0003-0906-0117 ; 0000-0001-7850-6894 ; 0000-0003-1330-0662 ; 0000-0002-9916-0332 ; 0000-0003-4083-8791</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fxen.12559$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fxen.12559$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31566261$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoon, Chang Ho</creatorcontrib><creatorcontrib>Choi, Se Hyun</creatorcontrib><creatorcontrib>Choi, Hyuk Jin</creatorcontrib><creatorcontrib>Lee, Hyun Ju</creatorcontrib><creatorcontrib>Kang, Hee Jung</creatorcontrib><creatorcontrib>Kim, Jong Min</creatorcontrib><creatorcontrib>Park, Chung‐Gyu</creatorcontrib><creatorcontrib>Choi, Kimyung</creatorcontrib><creatorcontrib>Kim, Hyunil</creatorcontrib><creatorcontrib>Ahn, Curie</creatorcontrib><creatorcontrib>Kim, Mee Kum</creatorcontrib><title>Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates</title><title>Xenotransplantation (Københaven)</title><addtitle>Xenotransplantation</addtitle><description>Background
We aimed to investigate (a) the long‐term survival of corneal grafts from α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pigs in non‐human primates as a primary outcome and (b) the effect of anti‐CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome.
Methods
Nine rhesus macaques undergoing full‐thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti‐CD20 antibody.
Results
Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7‐ month‐old) and younger (≤7‐month‐old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti‐αGal IgG/M levels were unchanged in both groups. At last examination, anti‐non‐Gal IgG was increased in the control group alone (P = .013).
Conclusions
The GTKOm pig corneal graft achieved long‐term survival when combined with anti‐CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.</description><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antigens, CD20 - immunology</subject><subject>anti‐CD20 antibody</subject><subject>B-Lymphocytes - physiology</subject><subject>CD20 antigen</subject><subject>complement</subject><subject>Complement component C3a</subject><subject>Cornea</subject><subject>Corneal Transplantation</subject><subject>Galactosyltransferases - genetics</subject><subject>Gene Knockout Techniques</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival</subject><subject>Heterografts - physiology</subject><subject>Hogs</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Intravenous administration</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes B</subject><subject>Monoclonal antibodies</subject><subject>non‐Gal</subject><subject>non‐human primate</subject><subject>Primates</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Tacrolimus</subject><subject>Transplantation, Heterologous</subject><subject>Xenografts</subject><subject>xenotransplantation</subject><subject>α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pig</subject><issn>0908-665X</issn><issn>1399-3089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10T1uFDEUB3ALgcgSKLgAskQDEpP4a7x2iaJAIq2gASndyOM8T5ydsRd7HNiOI9BwEC6SQ3CSONlAgYQbS34__W2_h9BzSg5oXYffIBxQ1rb6AVpQrnXDidIP0YJoohop27M99CTnS0IIb1X7GO1x2krJJF2gn6sYht_ff8yQJpxLuvJXZsTRYVfG8fb8wtt1gJyxjSlArdXL4pCMmzN2KU74-hd9w6sczGjsHPN2nJMJ2UEyGfAAAWpxHaJdxzLjyQdv5pIAb_yQsQ84xFDBRZlMwJvkJzNDfooeOTNmeHa_76PP744_HZ00q4_vT4_erhrLpNKNYK2xThjKqCZSaOO4sQoc72sTSC_Y8twyQawQrtfWGNODVEItHSx7YZXi--jVLneT4pcCee4mny2MowkQS-4Y01oIySWp9OU_9DKWFOrrOsZbyhQTglb1eqdsijkncN3dl9K2o6S7nVVX29fdzaraF_eJpZ_g_K_8M5wKDnfgqx9h-_-k7uz4wy7yBnqxpzE</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Yoon, Chang Ho</creator><creator>Choi, Se Hyun</creator><creator>Choi, Hyuk Jin</creator><creator>Lee, Hyun Ju</creator><creator>Kang, Hee Jung</creator><creator>Kim, Jong Min</creator><creator>Park, Chung‐Gyu</creator><creator>Choi, Kimyung</creator><creator>Kim, Hyunil</creator><creator>Ahn, Curie</creator><creator>Kim, Mee Kum</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1249-6181</orcidid><orcidid>https://orcid.org/0000-0001-7033-1102</orcidid><orcidid>https://orcid.org/0000-0001-7022-4331</orcidid><orcidid>https://orcid.org/0000-0003-2203-5709</orcidid><orcidid>https://orcid.org/0000-0001-9313-1322</orcidid><orcidid>https://orcid.org/0000-0002-7314-2267</orcidid><orcidid>https://orcid.org/0000-0003-0906-0117</orcidid><orcidid>https://orcid.org/0000-0001-7850-6894</orcidid><orcidid>https://orcid.org/0000-0003-1330-0662</orcidid><orcidid>https://orcid.org/0000-0002-9916-0332</orcidid><orcidid>https://orcid.org/0000-0003-4083-8791</orcidid></search><sort><creationdate>202001</creationdate><title>Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates</title><author>Yoon, Chang Ho ; Choi, Se Hyun ; Choi, Hyuk Jin ; Lee, Hyun Ju ; Kang, Hee Jung ; Kim, Jong Min ; Park, Chung‐Gyu ; Choi, Kimyung ; Kim, Hyunil ; Ahn, Curie ; Kim, Mee Kum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2689-425acf4a12190649af3ac8ef3b3990b427dc240c44fb9caaabe68487fe7b4c883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antigens, CD20 - immunology</topic><topic>anti‐CD20 antibody</topic><topic>B-Lymphocytes - physiology</topic><topic>CD20 antigen</topic><topic>complement</topic><topic>Complement component C3a</topic><topic>Cornea</topic><topic>Corneal Transplantation</topic><topic>Galactosyltransferases - genetics</topic><topic>Gene Knockout Techniques</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival</topic><topic>Heterografts - physiology</topic><topic>Hogs</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Intravenous administration</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes B</topic><topic>Monoclonal antibodies</topic><topic>non‐Gal</topic><topic>non‐human primate</topic><topic>Primates</topic><topic>Swine</topic><topic>Swine, Miniature</topic><topic>Tacrolimus</topic><topic>Transplantation, Heterologous</topic><topic>Xenografts</topic><topic>xenotransplantation</topic><topic>α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pig</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoon, Chang Ho</creatorcontrib><creatorcontrib>Choi, Se Hyun</creatorcontrib><creatorcontrib>Choi, Hyuk Jin</creatorcontrib><creatorcontrib>Lee, Hyun Ju</creatorcontrib><creatorcontrib>Kang, Hee Jung</creatorcontrib><creatorcontrib>Kim, Jong Min</creatorcontrib><creatorcontrib>Park, Chung‐Gyu</creatorcontrib><creatorcontrib>Choi, Kimyung</creatorcontrib><creatorcontrib>Kim, Hyunil</creatorcontrib><creatorcontrib>Ahn, Curie</creatorcontrib><creatorcontrib>Kim, Mee Kum</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Xenotransplantation (Københaven)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoon, Chang Ho</au><au>Choi, Se Hyun</au><au>Choi, Hyuk Jin</au><au>Lee, Hyun Ju</au><au>Kang, Hee Jung</au><au>Kim, Jong Min</au><au>Park, Chung‐Gyu</au><au>Choi, Kimyung</au><au>Kim, Hyunil</au><au>Ahn, Curie</au><au>Kim, Mee Kum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates</atitle><jtitle>Xenotransplantation (Københaven)</jtitle><addtitle>Xenotransplantation</addtitle><date>2020-01</date><risdate>2020</risdate><volume>27</volume><issue>1</issue><spage>e12559</spage><epage>n/a</epage><pages>e12559-n/a</pages><issn>0908-665X</issn><eissn>1399-3089</eissn><abstract>Background
We aimed to investigate (a) the long‐term survival of corneal grafts from α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pigs in non‐human primates as a primary outcome and (b) the effect of anti‐CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome.
Methods
Nine rhesus macaques undergoing full‐thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti‐CD20 antibody.
Results
Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7‐ month‐old) and younger (≤7‐month‐old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti‐αGal IgG/M levels were unchanged in both groups. At last examination, anti‐non‐Gal IgG was increased in the control group alone (P = .013).
Conclusions
The GTKOm pig corneal graft achieved long‐term survival when combined with anti‐CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31566261</pmid><doi>10.1111/xen.12559</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-1249-6181</orcidid><orcidid>https://orcid.org/0000-0001-7033-1102</orcidid><orcidid>https://orcid.org/0000-0001-7022-4331</orcidid><orcidid>https://orcid.org/0000-0003-2203-5709</orcidid><orcidid>https://orcid.org/0000-0001-9313-1322</orcidid><orcidid>https://orcid.org/0000-0002-7314-2267</orcidid><orcidid>https://orcid.org/0000-0003-0906-0117</orcidid><orcidid>https://orcid.org/0000-0001-7850-6894</orcidid><orcidid>https://orcid.org/0000-0003-1330-0662</orcidid><orcidid>https://orcid.org/0000-0002-9916-0332</orcidid><orcidid>https://orcid.org/0000-0003-4083-8791</orcidid></addata></record> |
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| subjects | Animals Animals, Genetically Modified Antibodies, Monoclonal - therapeutic use Antigens, CD20 - immunology anti‐CD20 antibody B-Lymphocytes - physiology CD20 antigen complement Complement component C3a Cornea Corneal Transplantation Galactosyltransferases - genetics Gene Knockout Techniques Graft Rejection - prevention & control Graft Survival Heterografts - physiology Hogs Humans Immunoglobulin G Intravenous administration Lymphocyte Activation Lymphocytes B Monoclonal antibodies non‐Gal non‐human primate Primates Swine Swine, Miniature Tacrolimus Transplantation, Heterologous Xenografts xenotransplantation α1,3‐galactosyltransferase gene‐knockout miniature (GTKOm) pig |
| title | Long‐term survival of full‐thickness corneal xenografts from α1,3‐galactosyltransferase gene‐knockout miniature pigs in non‐human primates |
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