Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Burlak, C.; Paris, L.L.; Lutz, A.J.; Sidner, R.A.; Estrada, J.; Li, P.; Tector, M.; Tector, A.J.

doi:10.1111/ajt.12744

Cited by 87Xenotransplantation and immune responseOrgan and Tissue Transplantation ResearchAnimal Genetics and Reproduction

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Open access

Burlak, C., Paris, L.L., Lutz, A.J., Sidner, R.A., Estrada, J., Li, P., Tector, M., Tector, A.J.·2014·American Journal of Transplantation

DOI 10.1111/ajt.12744PMC PMC4366649

Open this paper in CoChat — free account

Abstract

Xenotransplantation using genetically modified pig organs could solve the donor organ shortage problem. Two inactivated genes that make humans unique from pigs are GGTA1 and CMAH, the products of which produce the carbohydrate epitopes, aGal and Neu5Gc that attract preformed human antibody. When the GGTA1 and CMAH genes were deleted in pigs, human antibody binding was reduced in preliminary analysis. We analyzed the binding of human IgM and IgG from 121 healthy human serum samples for binding to GGTA1 KO and GGTA1/CMAH KO peripheral blood mononuclear cells (PBMCs). We analyzed a sub population for reactivity toward genetically modified pig PBMCs as compared to chimpanzee and human PBMCs. Deletion of the GGTA1 and CMAH genes in pigs improved the crossmatch results beyond those observed with chimpanzees. Sorting the 121 human samples tested against the GGTA1/CMAH KO pig PBMCs did not reveal a distinguishing feature such as blood group, age or gender. Modification of genes to make pig carbohydrates more similar to humans has improved the crossmatch with human serum significantly.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1111/ajt.12744

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Xenogeneic sialic acids are one of the leading non-α-gal antigens, participating in the rejection of xenografts.
“Xenogeneic sialic acids are one of the leading non-α-gal antigens, participating in the rejection of xenografts [133–135].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [134]
The Introduction (page unavailable) identifies Neu5Gc, a sialic acid found in pigs but not humans, as a significant xenoantigen. The Discussion (page unavailable) reports improved human-antibody crossmatches after Neu5Gc was removed. The paper does not establish that xenogeneic sialic acids generally are leading non-α-gal antigens or directly demonstrate their participation in xenograft rejection. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Exposing cells of GT-CMAH knockout pigs (which lack expression of α-gal and Neu5Gc epitopes) to human serum demonstrates fewer antigen-antibody reactions.
“Exposing cells of GT-CMAH knockout pigs (which lack expression of α-gal and Neu5Gc epitopes) to human serum demonstrates fewer antigen-antibody reactions [133, 134].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [134]
α-Gal and the nonhuman sialic acid Neu5Gc represent the major xenoantigens that must be bypassed for xenotransplantation into humans, and α-Gal- and Neu5Gc-double null pigs have recently been generated.
“glycans like ɑ -Gal and the nonhuman sialic acid Neu5Gc represent the major xenoantigens that must be bypassed, to pursue the goal of xeno- (pig organ) transplantation into humans. In pursuit of this dif fi cult goal, ɑ -Galand Neu5Gc-double null pigs have recently been generated (980 -983).”
From Biological roles of glycans (2017) · cites this paper as [981]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Production of α-1,3-Galactosyltransferase Knockout Pigs by Nuclear Transfer Cloning
Lai, L., Kolber, D. L., Park, K., Cheong, H.-T., Greenstein, J. L., Im, G., Samuel, M., Bonk, A., Rieke, A., Day, B. N., et al. (2002) · Science · doi:10.1126/science.1068228 · Cited by 1,332 · see citing works
Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue
Yamada, K., Yazawa, K., Shimizu, A., Iwanaga, T., Hisashi, Y., Nuhn, M. G., O'Malley, P., Nobori, S., Vagefi, P. A., Patience, C., et al. (2004) · Nature Medicine · doi:10.1038/nm1172 · Cited by 609 · see citing works
Production of α-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations
Kolber, D. L., Lai, L., Watt, S. R., Denaro, M., Arn, S., Augenstein, M. L., Betthauser, J. M., Carter, D. B., Greenstein, J. L., Hao, Y., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307819101 · Cited by 458 · see citing works
Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases
Hauschild‐Quintern, J., Petersen, B., Santiago, Y., Queisser, A. L., Carnwath, J. W., Lucas‐Hahn, A., Zhang, L., Meng, X., Gregory, P. D., Schwinzer, R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106422108 · Cited by 366 · see citing works
Experience in Renal Transplantation
Starzl, T. E. (1965) · The American Journal of the Medical Sciences · doi:10.1097/00000441-196505000-00064 · Cited by 364 · see citing works
Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys
Chen, G., Qian, H., Starzl, T. E., Sun, H., Garcia, B. M., Wang, X., Wise, Y., Liu, Y., Xiang, Y., Copeman, L. S., et al. (2005) · Nature Medicine · doi:10.1038/nm1330 · Cited by 357 · see citing works
Renal Heterotransplmtation in Man
REEMTSHA, K., McCracken, B. H., & SCHEGEL, J. U. (1964) · Annals of Surgery · doi:10.1097/00000658-196409000-00006 · Cited by 335 · see citing works
Double knockout pigs deficient in <scp>N</scp> ‐glycolylneuraminic acid and <scp>G</scp> alactose α‐1,3‐ <scp>G</scp> alactose reduce the humoral barrier to xenotransplantation
Lutz, A. J., Li, P., Estrada, J. L., Sidner, R. A., Chihara, R. K., Downey, S. M., Burlak, C., Wang, Z., Reyes, L. M., Ivary, B., et al. (2013) · Xenotransplantation · doi:10.1111/xen.12019 · Cited by 294 · see citing works
Self-citation
Efficient nonmeiotic allele introgression in livestock using custom endonucleases
Tan, W. S., Carlson, D. F., Lancto, C. A., Garbe, J., Webster, D. A., Hackett, P. B., & Fahrenkrug, S. C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310478110 · Cited by 279 · see citing works
The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.
Lin, S. S., Weidner, B. C., Byrne, G. W., Diamond, L. E., Lawson, J. H., Hoopes, C. W., Daniels, L. J., Daggett, C. W., Parker, W., Harland, R. C., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2134 · Cited by 273 · see citing works
RENAL HETEROTRANSPLANTATION FROM BABOON TO MAN
Stabzl, T. E., Marchioro, T. L., Peters, G. N., Kiekpatrick, C. H., Wilson, W. E., Porter, K. A., Rifkind, D., Ogden, D. A., Hitchcock, C. R., & Waddell, W. R. (1964) · Transplantation · doi:10.1097/00007890-196411000-00009 · Cited by 237 · see citing works
Intravenous Gammaglobulin (IVIG): A Novel Approach to Improve Transplant Rates and Outcomes in Highly HLA-Sensitized Patients
Jordan, S. C., Vo, A. A., Peng, A., Toyoda, M., & Tyan, D. B. (2006) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.01214.x · Cited by 179 · see citing works
Thrombotic Microangiopathy Associated with Humoral Rejection of Cardiac Xenografts from α1,3-Galactosyltransferase Gene-Knockout Pigs in Baboons
Shimizu, A., Hisashi, Y., Kuwaki, K., Tseng, Y., Dor, F. J. M. F., Houser, S. L., Robson, S. C., Schuurman, H., Cooper, D. K. C., Sachs, D. H., et al. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.070672 · Cited by 146 · see citing works
Experience in Renal Transplantation
Kelly, W. D. (1964) · JAMA · doi:10.1001/jama.1964.03070200127044 · Cited by 143 · see citing works
Long-Term IgG Response to Porcine Neu5Gc Antigens without Transmission of PERV in Burn Patients Treated with Porcine Skin Xenografts
Scobie, L., Padler‐Karavani, V., Bas‐Bernardet, S. L., Crossan, C., Bláha, J., Matoušková, M., Hector, R. D., Cozzi, E., Vanhove, B., Charreau, B. L., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301195 · Cited by 127 · see citing works
Identification of New Carbohydrate and Membrane Protein Antigens in Cardiac Xenotransplantation
Byrne, G. W., Stalboerger, P. G., Du, Z., Davis, T. R., & McGregor, C. G. A. (2010) · Transplantation · doi:10.1097/tp.0b013e318203c27d · Cited by 121 · see citing works
The Molecular Basis for Galα(1,3)Gal Expression in Animals with a Deletion of the α1,3Galactosyltransferase Gene
Milland, J., Christiansen, D., Lazarus, B. D., Taylor, S. G., Xing, P., & Sandrin, M. S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2448 · Cited by 110 · see citing works
Pig cells that lack the gene for α1-3 galactosyltransferase express low levels of the gal antigen
Sharma, A., Naziruddin, B., Cui, C., Martin, M. J., Xu, H. M., Wan, H., Lei, Y., Harrison, C., Yin, J., Okabe, J., et al. (2003) · Transplantation · doi:10.1097/01.tp.0000053615.98201.77 · Cited by 100 · see citing works
Production of biallelic CMP-Neu5Ac hydroxylase knock-out pigs
Kwon, D., Lee, K., Kang, M., Choi, Y., Park, C., Whyte, J. J., Brown, A. N., Kim, J.-H., Samuel, M., Mao, J., et al. (2013) · Scientific Reports · doi:10.1038/srep01981 · Cited by 95 · see citing works
Increased Immunosuppression, Not Anticoagulation, Extends Cardiac Xenograft Survival
Byrne, G. W., Davies, W. R. O., Oi, K., Rao, V. P., Teotia, S. S., Ricci, D., Tazelaar, H. D., Walker, R. C., Logan, J. S., & McGregor, C. G. A. (2006) · Transplantation · doi:10.1097/01.tp.0000251387.40499.0f · Cited by 63 · see citing works
Human-specific evolution of sialic acid targets: Explaining the malignant malaria mystery?
Varki, A., & Gagneux, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908196106 · Cited by 62 · see citing works
Structural characterization of α1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies
Diswall, M., Ångström, J., Karlsson, H., Phelps, C. J., Ayares, D., Teneberg, S., & Breimer, M. E. (2010) · Xenotransplantation · doi:10.1111/j.1399-3089.2009.00564.x · Cited by 59 · see citing works
Kidney xenotransplantation
Cowan, P. J., Cooper, D. K. C., & d’Apice, A. J. F. (2013) · Kidney International · doi:10.1038/ki.2013.381 · Cited by 51 · see citing works
Biallelic knockout of the α-1,3 galactosyltransferase gene in porcine liver-derived cells using zinc finger nucleases
Li, P., Estrada, J., Burlak, C., & Tector, A. J. (2012) · Journal of Surgical Research · doi:10.1016/j.jss.2012.06.035 · Cited by 47 · see citing works
Self-citation
α1,3Galactosyltransferase knockout pigs produce the natural anti‐Gal antibody and simulate the evolutionary appearance of this antibody in primates
Galili, U. (2013) · Xenotransplantation · doi:10.1111/xen.12051 · Cited by 45 · see citing works
Identification of human preformed antibody targets in GTKO pigs
Burlak, C., Wang, Z., Chihara, R., Lutz, A. J., Wang, Y., Estrada, J. L., & Tector, A. J. (2012) · Xenotransplantation · doi:10.1111/j.1399-3089.2012.00695.x · Cited by 33 · see citing works
Self-citation
Complete absence of the αGal xenoantigen and isoglobotrihexosylceramide in α1,3galactosyltransferase knock‐out pigs
Yung, G. P., Li, Y., Borsig, L., Millard, A., Karpova, M. B., Zhou, D., & Seebach, J. D. (2012) · Xenotransplantation · doi:10.1111/j.1399-3089.2012.00705.x · Cited by 29 · see citing works
PATHOLOGICAL CHANGES IN SIX TREATED BABOON‐TO‐MAN RENAL HETEROTRANSPLANTS
Porter, K. A., Marchioro, T. L., & Starzl, T. E. (1965) · British Journal of Urology · doi:10.1111/j.1464-410x.1965.tb09599.x · Cited by 12 · see citing works

Flagged first, then by citations

1 of the 29 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

[5]Hardy MA Xenograft 25 1989 Amsteram Elsevier Science Publishers B.V. 1
[29]Byrne GW Stalboerger PG Du Z Davis TR McGregor CGA Identification of new carbohydrate and membrane protein antigens in cardiac xenotransplantation 2011 2 15 91 3 287 292 Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=21119562&retmode=ref&cmd=prlinks PMC10022691 21119562

Sorted by citations

Biological roles of glycans
Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635 · see citing works
“In pursuit of this difficult goal, ɑ-Galand Neu5Gc-double null pigs have recently been generated (980) (981) (982) (983) .”
Background
Evaluation of human and non‐human primate antibody binding to pig cells lacking GGTA 1/ CMAH /β4Gal NT 2 genes
Estrada, J. L., Martens, G., Li, P., Adams, A. B., Newell, K. A., Ford, M. L., Butler, J. R., Sidner, R. A., Tector, A. J., & Tector, A. J. (2015) · Xenotransplantation · doi:10.1111/xen.12161 · Cited by 421 · see citing works
Self-citation
Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine
Kasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316 · see citing works
Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs
Martens, G. R., Reyes, L. M., Butler, J. R., Ladowski, J. M., Estrada, J. L., Sidner, R. A., Eckhoff, D. E., Tector, M., & Tector, A. J. (2017) · Transplantation · doi:10.1097/tp.0000000000001646 · Cited by 231 · see citing works
Self-citation
Pre‐transplant antibody screening and anti‐CD154 costimulation blockade promote long‐term xenograft survival in a pig‐to‐primate kidney transplant model
Higginbotham, L. B., Mathews, D., Breeden, C. P., Song, M., Farris, A. B., Larsen, C. P., Ford, M. L., Lutz, A. J., Tector, M. F., Newell, K. A., et al. (2015) · Xenotransplantation · doi:10.1111/xen.12166 · Cited by 222 · see citing works
Self-citation
The role of genetically engineered pigs in xenotransplantation research
Cooper, D. K. C., Ekser, B., Ramsoondar, J., Phelps, C. J., & Ayares, D. (2015) · The Journal of Pathology · doi:10.1002/path.4635 · Cited by 221 · see citing works
Xenotransplantation: Current Status in Preclinical Research
Lu, T., Yang, B., Wang, R., & Qin, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03060 · Cited by 215 · see citing works
Transplanting organs from pigs to humans
Sykes, M., & Sachs, D. H. (2019) · Science Immunology · doi:10.1126/sciimmunol.aau6298 · Cited by 191 · see citing works
Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid
Alisson-Silva, F., Kawanishi, K., & Varki, A. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.07.002 · Cited by 156 · see citing works
The pathobiology of pig‐to‐primate xenotransplantation: a historical review
Cooper, D. K. C., Ezzelarab, M., Hara, H., Iwase, H., Lee, W., Wijkstrom, M., & Bottino, R. (2016) · Xenotransplantation · doi:10.1111/xen.12219 · Cited by 139 · see citing works
From “Serum Sickness” to “Xenosialitis”: Past, Present, and Future Significance of the Non-human Sialic Acid Neu5Gc
Dhar, C., Sasmal, A., & Varki, A. P. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00807 · Cited by 122 · see citing works
The immunological barriers to xenotransplantation
Vadori, M., & Cozzi, E. (2015) · Tissue Antigens · doi:10.1111/tan.12669 · Cited by 93 · see citing works
Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss of N‐Glycolylneuraminic Acid
Okerblom, J., & Varki, A. P. (2017) · ChemBioChem · doi:10.1002/cbic.201700077 · Cited by 80 · see citing works
Current status of xenotransplantation research and the strategies for preventing xenograft rejection
Zhou, Q., Li, T., Wang, K., Zhang, Q., Geng, Z., Deng, S., Cheng, C., & Wang, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.928173 · Cited by 66 · see citing works
The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation
Tector, A. J., Mosser, M., Tector, M., & Bach, J.-M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00622 · Cited by 60 · see citing works
Self-citation
Porcine genome engineering for xenotransplantation
Niu, D., Ma, X., Yuan, T., Niu, Y., Xu, Y., Sun, Z., Yuan, P., Li, W., Zhang, J., Wang, T., et al. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.04.001 · Cited by 57 · see citing works
Generation of GGTA1 Mutant Pigs by Direct Pronuclear Microinjection of CRISPR/Cas9 Plasmid Vectors
Chuang, C.-K., Chen, C., Huang, C.-L., Su, Y.-H., Peng, S.-H., Lin, T.-Y., Tai, H., Yang, T., & Tu, C. (2016) · Animal Biotechnology · doi:10.1080/10495398.2016.1246453 · Cited by 53 · see citing works
Silencing porcine genes significantly reduces human-anti-pig cytotoxicity profiles: an alternative to direct complement regulation
Butler, J. R., Martens, G. R., Estrada, J. L., Reyes, L. M., Ladowski, J. M., Galli, C., Perota, A., Cunningham, C. M., Tector, M. F., & Tector, A. J. (2016) · Transgenic Research · doi:10.1007/s11248-016-9958-0 · Cited by 52 · see citing works
Self-citation
Initial in vitro studies on tissues and cells from GTKO/CD46/NeuGcKO pigs
Lee, W., Hara, H., Ezzelarab, M. B., Iwase, H., Bottino, R., Long, C. E., Ramsoondar, J., Ayares, D., & Cooper, D. K. C. (2016) · Xenotransplantation · doi:10.1111/xen.12229 · Cited by 47 · see citing works
Evolution of sialic acids: Implications in xenotransplant biology
Paul, A., & Padler‐Karavani, V. (2018) · Xenotransplantation · doi:10.1111/xen.12424 · Cited by 45 · see citing works
Perspectives on the Optimal Genetically Engineered Pig in 2018 for Initial Clinical Trials of Kidney or Heart Xenotransplantation
Cooper, D. K. C., Ezzelarab, M. B., Iwase, H., & Hara, H. (2018) · Transplantation · doi:10.1097/tp.0000000000002443 · Cited by 45 · see citing works
Recent advances in understanding xenotransplantation: implications for the clinic
Cooper, D. K. C., & Bottino, R. (2015) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.1083861 · Cited by 44 · see citing works
β Cell Replacement Therapy
Schuetz, C., Anazawa, T., Cross, S. E., Labriola, L., Meier, R. P. H., Redfield, R. R., Scholz, H., Stock, P. G., & Zammit, N. W. (2017) · Transplantation · doi:10.1097/tp.0000000000001937 · Cited by 43 · see citing works
Optimizing sgRNA length to improve target specificity and efficiency for the GGTA1 gene using the CRISPR/Cas9 gene editing system
Matson, A. W., Hosny, N., Swanson, Z. A., Hering, B. J., & Burlak, C. (2019) · PLoS ONE · doi:10.1371/journal.pone.0226107 · Cited by 40 · see citing works
Self-citation
Type 1 diabetes and engineering enhanced islet transplantation
Jeyagaran, A., Lu, C., Zbinden, A., Birkenfeld, A. L., Brucker, S. Y., & Layland, S. L. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114481 · Cited by 41 · see citing works
The Sda and Cad glycan antigens and their glycosyltransferase, β1,4Gal<scp>NA</scp>cT‐<scp>II</scp>, in xenotransplantation
Zhao, C., Cooper, D. K. C., Dai, Y., Hara, H., Cai, Z., & Mou, L. (2018) · Xenotransplantation · doi:10.1111/xen.12386 · Cited by 39 · see citing works
First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes—Chapter 6: patient selection for pilot clinical trials of islet xenotransplantation
Hering, B. J., & O’Connell, P. J. (2016) · Xenotransplantation · doi:10.1111/xen.12228 · Cited by 36 · see citing works
Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Gene Editing Technique in Xenotransplantation
Kararoudi, M. N., Hejazi, S. S., Elmas, E., Hellström, M., Kararoudi, M. N., Padma, A. M., Lee, D. A., & Dolatshad, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01711 · Cited by 37 · see citing works
The respective relevance of sensitization to alloantigens and xenoantigens in pig organ xenotransplantation
Cooper, D. K. C., Habibabady, Z. A., Kinoshita, K., Hara, H., & Pierson, R. N. (2022) · Human Immunology · doi:10.1016/j.humimm.2022.06.003 · Cited by 35 · see citing works
Neu5Gc and α1-3 GAL Xenoantigen Knockout Does Not Affect Glycemia Homeostasis and Insulin Secretion in Pigs
Salama, A., Mosser, M., Lévêque, X. T., Perota, A., Judor, J., Danna, C., Pogu, S., Moure, A. G., Jégou, D., Gaide, N., et al. (2017) · Diabetes · doi:10.2337/db16-1060 · Cited by 34 · see citing works
Immune Responses of HLA Highly Sensitized and Nonsensitized Patients to Genetically Engineered Pig Cells
Zhang, Z., Hara, H., Long, C. E., Iwase, H., Qi, H., Macedo, C., Mangiola, M., Zeevi, A., Ezzelarab, M. B., Ayares, D., et al. (2017) · Transplantation · doi:10.1097/tp.0000000000002060 · Cited by 32 · see citing works
Cardiac Xenotransplantation: Progress in Preclinical Models and Prospects for Clinical Translation
Singh, A. K., Goerlich, C. E., Shah, A. M., Zhang, T., Tatarov, I., Ayares, D., Horvath, K. A., & Mohiuddin, M. M. (2022) · Transplant International · doi:10.3389/ti.2022.10171 · Cited by 33 · see citing works
Models of immunogenicity in preclinical assessment of tissue engineered heart valves
Ground, M., Waqanivavalagi, S., Walker, R., Milsom, P., & Cornish, J. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.05.049 · Cited by 31 · see citing works
Human antibody reactivity against xenogeneic N‐glycolylneuraminic acid and galactose‐α‐1,3‐galactose antigen
Hurh, S., Kang, B., Choi, I., Cho, B., Lee, E. M., Kim, H., Kim, Y. J., Chung, Y. S., Jeong, J. C., Hwang, J., et al. (2016) · Xenotransplantation · doi:10.1111/xen.12239 · Cited by 31 · see citing works
Emerging Technologies in Organ Preservation, Tissue Engineering and Regenerative Medicine: A Blessing or Curse for Transplantation?
Messner, F., Guo, Y., Etra, J. W., & Brandacher, G. (2019) · Transplant International · doi:10.1111/tri.13432 · Cited by 29 · see citing works
Eliminating Xenoantigen Expression on Swine RBC
Wang, Z., Martens, G. R., Blankenship, R. L., Sidner, R. A., Li, P., Estrada, J. L., Tector, M. F., & Tector, A. J. (2016) · Transplantation · doi:10.1097/tp.0000000000001302 · Cited by 29 · see citing works
Self-citation
Immunogenicity of Renal Microvascular Endothelial Cells From Genetically Modified Pigs
Wang, Z., Li, P., Butler, J. R., Blankenship, R. L., Downey, S. M., Montgomery, J. B., Nagai, S., Estrada, J. L., Tector, M. F., & Tector, A. J. (2016) · Transplantation · doi:10.1097/tp.0000000000001070 · Cited by 26 · see citing works
Self-citation
Genetically-engineered pigs as sources for clinical red blood cell transfusion: What pathobiological barriers need to be overcome?
Smood, B. F., Hara, H., Schoel, L. J., & Cooper, D. K. C. (2019) · Blood Reviews · doi:10.1016/j.blre.2019.01.003 · Cited by 26 · see citing works
HLA-G1+ Expression in GGTA1KO Pigs Suppresses Human and Monkey Anti-Pig T, B and NK Cell Responses
Rao, J. S., Hosny, N., Kumbha, R., Naqvi, R. A., Singh, A. R., Swanson, Z. A., Levy, H., Matson, A. W., Steinhoff, M., Forneris, N., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.730545 · Cited by 25 · see citing works
Self-citation
What Have We Learned From In Vitro Studies About Pig-to-primate Organ Transplantation?
Hara, H., Yamamoto, T., Wei, H., & Cooper, D. K. C. (2022) · Transplantation · doi:10.1097/tp.0000000000004458 · Cited by 25 · see citing works
In vitro characterization of neonatal, juvenile, and adult porcine islet oxygen demand, β‐cell function, and transcriptomes
Smith, K. E., Purvis, W. G., Davis, M. A., Min, C. G., Cooksey, A. M., Weber, C. S., Jandová, J., Price, N. D., Molano, D. S., Stanton, J. B., et al. (2018) · Xenotransplantation · doi:10.1111/xen.12432 · Cited by 25 · see citing works
In Search of the Ideal Valve: Optimizing Genetic Modifications to Prevent Bioprosthetic Degeneration
Smood, B. F., Hara, H., Cleveland, D. C., & Cooper, D. K. C. (2019) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2019.01.054 · Cited by 25 · see citing works
N‐glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig‐to‐human xenoperfusion model
Cimeno, A., Hassanein, W., French, B. M., Powell, J. M., Burdorf, L., Goloubeva, O. G., Cheng, X., Parsell, D. M., Ramsoondar, J., Kuravi, K. V., et al. (2017) · Xenotransplantation · doi:10.1111/xen.12339 · Cited by 24 · see citing works
Update on cellular encapsulation
Smith, K. E., Johnson, R. C., & Papas, K. K. (2018) · Xenotransplantation · doi:10.1111/xen.12399 · Cited by 24 · see citing works
Expression of NeuGc on Pig Corneas and Its Potential Significance in Pig Corneal Xenotransplantation
Lee, W., Miyagawa, Y., Long, C. E., Ekser, B., Walters, E. M., Ramsoondar, J., Ayares, D., Tector, A. J., Cooper, D. K. C., & Hara, H. (2015) · Cornea · doi:10.1097/ico.0000000000000635 · Cited by 23 · see citing works
Self-citation
A desirable transgenic strategy using GGTA1 endogenous promoter-mediated knock-in for xenotransplantation model
Ko, N., Shim, J., Kim, H.-J., Lee, Y., Park, J., Kwak, K., Lee, J.-W., Jin, D. I., Kim, H., & Choi, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-13536-z · Cited by 23 · see citing works
Genetic engineering of porcine endothelial cell lines for evaluation of human-to-pig xenoreactive immune responses
Li, P., Walsh, J., Lopez, K., Isidan, A., Zhang, W., Chen, A. M., Goggins, W. C., Higgins, N. G., Liu, J., Brutkiewicz, R. R., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-92543-y · Cited by 19 · see citing works
Self-citation
High-mannose type N-glycans with core fucosylation and complex-type N-glycans with terminal neuraminic acid residues are unique to porcine islets
Nanno, Y., Shajahan, A., Sonon, R. N., Azadi, P., Hering, B. J., & Burlak, C. (2020) · PLoS ONE · doi:10.1371/journal.pone.0241249 · Cited by 17 · see citing works
Self-citation
In vitro exposure of pig neonatal isletlike cell clusters to human blood
Nagaraju, S., Bertera, S., Tanaka, T., Hara, H., Rayat, G. R., Wijkstrom, M. N., Ayares, D., Trucco, M., Cooper, D. K. C., & Bottino, R. (2015) · Xenotransplantation · doi:10.1111/xen.12178 · Cited by 17 · see citing works
Developments in kidney xenotransplantation
Xu, H., & He, X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1242478 · Cited by 16 · see citing works
Clinical Xenotransplantation, a Closer Reality: Literature Review
Aristizábal, A. M., Caicedo, L. A., Martínez, J. M., Moreno, M., & Echeverri, G. J. (2017) · Cirugía Española (English Edition) · doi:10.1016/j.cireng.2017.03.007 · Cited by 16 · see citing works
Xenotrasplantes, una realidad cercana en la práctica clínica: revisión de la literatura
Aristizábal, A. M., Caicedo, L. A., Martínez, J. M., Moreno, M., & Echeverri, G. J. (2017) · Cirugía Española · doi:10.1016/j.ciresp.2016.12.008 · Cited by 15 · see citing works
Serum Antibody Binding and Cytotoxicity to Pig Cells in Chinese Subjects: Relevance to Clinical Renal Xenotransplantation
Li, T., Feng, H., Du, J., Xia, Q., Cooper, D. K. C., Jiang, H., He, S., Pan, D., Chen, G., & Wang, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.844632 · Cited by 14 · see citing works
Vital, Porcine, Gal-Knockout Skin Transplants Provide Efficacious Temporary Closure of Full-Thickness Wounds: Good Laboratory Practice-Compliant Studies in Nonhuman Primates
Holzer, P. W., Adkins, J., Moulton, K., Zhu, L., Monroy, R. L., & Cetrulo, C. L. (2020) · Journal of Burn Care & Research · doi:10.1093/jbcr/irz124 · Cited by 14 · see citing works
Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth
Singireddy, S., Tully, A., Galindo, J., Ayares, D., Singh, A. K., & Mohiuddin, M. M. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01978-4 · Cited by 13 · see citing works
The fate of human platelets exposed to porcine renal endothelium: a single-pass model of platelet uptake in domestic and genetically modified porcine organs
Butler, J. R., Martens, G. R., Li, P., Wang, Z., Estrada, J. L., Ladowski, J. M., Tector, M., & Tector, A. J. (2015) · Journal of Surgical Research · doi:10.1016/j.jss.2015.08.034 · Cited by 10 · see citing works
Self-citation
Highly efficient biocatalytic cascade for the diversity-oriented synthesis of complex blood group Sd a antigens
Zhong, K., Ye, J., Zhu, X., Cao, H., & Liu, C. (2020) · Green Chemistry · doi:10.1039/d0gc02971h · Cited by 10 · see citing works
Immune disguise: the mechanisms of Neu5Gc inducing autoimmune and transplant rejection
Ding, F., Lin, Y.-F., Liu, G., Liu, Y., Gao, F., Liu, Q., Zhang, Z., & Weng, S. (2022) · Genes and Immunity · doi:10.1038/s41435-022-00182-8 · Cited by 9 · see citing works
An Overview of the Importance and Value of Porcine Species in Sialic Acid Research
Ogun, O. J., Thaller, G. E., & Becker, D. (2022) · Biology · doi:10.3390/biology11060903 · Cited by 8 · see citing works
Evaluation of Physiological Integrity in Six‐Gene‐Edited Bama Miniature Pigs as a Model for Xenotransplantation
Peng, W. C., Zhai, Y. Y., Li, M. K., Zhang, C., Du, J. X., Jiang, Y., Pan, D. K., & Wu, J. W. (2025) · Biotechnology Journal · doi:10.1002/biot.70030 · Cited by 7 · see citing works
The impact of serum incubation time on IgM/IgG binding to porcine aortic endothelial cells
Zhang, Z., Gao, B., Zhao, C., Long, C. E., Qi, H., Ezzelarab, M. B., Cooper, D. K. C., & Hara, H. (2017) · Xenotransplantation · doi:10.1111/xen.12312 · Cited by 7 · see citing works
Intestine specific regulation of pig cytidine-5′-monophospho-N-acetylneuraminic acid hydroxylase gene for N-glycolylneuraminic acid biosynthesis
Song, K., Kwak, C.-H., Chung, T., Ha, S., Park, J., Ha, K., Cho, S.-H., Lee, Y., & Kim, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-40522-9 · Cited by 6 · see citing works
Immunoglobulin M and Immunoglobulin G Subclass Distribution of Anti-galactose-Alpha-1,3-Galactose and Anti-N-Glycolylneuraminic Acid Antibodies in Healthy Korean Adults
Lee, E. J., Lee, H., Park, E. M., Kang, H. J., Kim, S. J., & Park, C. (2021) · Transplantation Proceedings · doi:10.1016/j.transproceed.2021.01.011 · Cited by 6 · see citing works
Genetically Engineered Large Animals in Biomedicine
Wolf, E., Kind, A., Aigner, B., & Schnieke, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-92348-2_9 · Cited by 6 · see citing works
Profiling natural serum antibodies of non‐human primates with a carbohydrate antigen microarray
Nanno, Y., Sterner, E., Gildersleeve, J. C., Hering, B. J., & Burlak, C. (2019) · Xenotransplantation · doi:10.1111/xen.12567 · Cited by 5 · see citing works
Self-citation
Xenotransplantation and Glycomedicine
Miyagawa, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14885-1 · Cited by 5 · see citing works
Pathological features in ‘humanized’ neonatal pig
Choe, H. M., Luo, Z., Kang, J., Oh, M. J., An, H. J., & Yin, X. (2021) · Animal Biotechnology · doi:10.1080/10495398.2021.1962896 · Cited by 4 · see citing works
Human anti‐α‐fucose antibodies are xenoreactive toward GGTA1/CMAH knockout pigs
Burlak, C., Taylor, R. T., Wang, Z., & Tector, A. J. (2020) · Xenotransplantation · doi:10.1111/xen.12629 · Cited by 4 · see citing works
Self-citation
Hemolysis-induced hepatic ferroptosis following xenotransfusion of genetically modified pig red blood cells
Shin, H.-Y., Lee, J. Y., Jang, Y.-J., Kim, H.-S., Park, S. R., Kang, G.-H., Shim, J., Ko, N., & Hwang, J. H. (2025) · Scientific Reports · doi:10.1038/s41598-025-30021-5 · Cited by 3 · see citing works
Alteration of γδ T cell subsets in non‐human primates transplanted with GGTA1 gene‐deficient porcine blood vessels
Lee, S., Chung, Y. S., Lee, K. W., Choi, M., Sonn, C. H., Oh, W. J., Hong, H. G., Shim, J., Choi, K., Kim, S. J., et al. (2023) · Xenotransplantation · doi:10.1111/xen.12838 · Cited by 3 · see citing works
Molecular Structural Analysis of Porcine CMAH–Native Ligand Complex and High Throughput Virtual Screening to Identify Novel Inhibitors
Ogun, O. J., Thaller, G. E., & Becker, D. (2023) · Pathogens · doi:10.3390/pathogens12050684 · Cited by 3 · see citing works
Comprehensive methylomes and transcriptomes of tissue-specific and body-size associated genes in miniature pigs
Kim, S., Kang, D., Jang, S., Chai, H., Kim, J., & Park, W. (2025) · Gene · doi:10.1016/j.gene.2025.149658 · Cited by 2 · see citing works
T cell-mediated immune responses in xenotransplantation: mechanisms and therapeutic strategies
Wang, Z., & Liu, G. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1767840 · Cited by 2 · see citing works
Modifying the Glycome in Pigs for Xenotransplantation
Cowan, P. J., & Rieben, R. (2016) · Transplantation · doi:10.1097/tp.0000000000001073 · Cited by 2 · see citing works
Modern xenotransplantation: rewiring glycan-mediated immunogenicity via genome-glycome convergence
Wang, M., Wang, Q., Liu, Y., Xu, J., Su, Y., Bai, H., Wang, Y., & Dong, J. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2025.106109 · Cited by 1 · see citing works
Overcoming xenotransplantation barriers through gene editing and immunomodulation
Tully, A., Singh, A. K., Galindo, J., Griffith, B. P., & Mohiuddin, M. M. (2026) · Nature Reviews Bioengineering · doi:10.1038/s44222-026-00412-y · Cited by 1 · see citing works
Swine Leukocyte Antigen-12 Behaves Like a Swine Leukocyte Antigen Classical Class I Protein and is a Potential Xenoantigen in Humans
Gennuso, V. N., Wang, Z., Reyes, L. M., Tector, M., & Tector, A. J. (2026) · Transplantation Direct · doi:10.1097/txd.0000000000001948 · Cited by 1 · see citing works
Self-citation
Cardiac xenotransplantation
Banks, C. A., Cooper, D. K. C., Iwase, H., Hara, H., Cleveland, D. C., & Ekser, B. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813706-2.00009-9 · Cited by 1 · see citing works
The future of transgenic farm animal production with emphasis on pigs.
Petersen, B., & Niemann, H. J. (2015) · CABI Reviews · doi:10.1079/pavsnnr20149044
Histocompatibility Testing for Xenotransplantation
Ladowski, J. M., & Martens, G. R. (2020) · Springer eBooks · doi:10.1007/978-3-030-49127-7_18
The Pathobiology of Pig-to-Primate Xeno.: A Historical Review
Cooper, D., Ezzelarab, M., Hara, H., Iwase, H., Lee, W., Wijkstrom, M., & Bottino, R. (2020) · Springer eBooks · doi:10.1007/978-3-030-49127-7_2
Xenotransplantation 1.0 to 2.0
Haque, O. J., Cloonan, D. J., McIntosh, E. E., & Ferran, C. J. (2020) · Springer eBooks · doi:10.1007/978-3-030-55244-2_18
Gentechnisch veränderte Großtiere in der Biomedizin
Wolf, E., Kind, A., Aigner, B., & Schnieke, A. (2023) · Springer eBooks · doi:10.1007/978-3-031-26042-1_9
Generation of Cloned Sheep Lacking Galactose‐α1,3‐Galactose and N‐Glycolylneuraminic Acid Antigens
Appleby, S. J., Fermin, L., McLean, Z. L., Delaney, S., Wagner, S., Genova, C. D., Wei, J., Meng, F., Wells, D. N., & Oback, B. J. (2026) · Xenotransplantation · doi:10.1111/xen.70134
Cardiac Xenotransplantation: Progress Towards Clinical Reality
Mohiuddin, M. M., Galindo, J., Tully, A., Singh, A. K., & Griffith, B. P. (2026) · Springer eBooks · doi:10.1007/978-3-032-12629-0_12
Neu5Gc and beyond: sialylation at the innate immune and thromboinflammatory interface of xenotransplantation
Kim, J. Y. (2026) · Frontiers in Transplantation · doi:10.3389/frtra.2026.1968710
Glycosylation in Quality and Safety of Therapeutic Proteins
Matsumoto, Y., Kim, J., McKenna, K. R., Biel, T. G., Kirshner, S., Falkowski, V. M., & Ju, T. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100163

Evaluation of human and non‐human primate antibody binding to pig cells lacking GGTA 1/ CMAH /β4Gal NT 2 genes
Estrada, J. L., Martens, G., Li, P., Adams, A. B., Newell, K. A., Ford, M. L., Butler, J. R., Sidner, R. A., Tector, A. J., & Tector, A. J. (2015) · Xenotransplantation · doi:10.1111/xen.12161 · Cited by 421 · see citing works
Self-citation
Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non‐human primates
Wang, Z., Burlak, C., Estrada, J. L., Li, P., Tector, M. F., & Tector, A. J. (2014) · Xenotransplantation · doi:10.1111/xen.12106 · Cited by 64 · see citing works
Self-citation
Generation of the GGTA1/CMAH/hCD46 Genetically Modified Pigs for Xenotransplantation
Kim, H.-J., Shim, J., Ko, N., Lee, Y., Park, J., & Choi, K. (2017) · Reproductive & Developmental Biology(Supplement)
N‐linked glycan profiling of GGTA 1/ CMAH knockout pigs identifies new potential carbohydrate xenoantigens
Burlak, C., Bern, M. W., Brito, A. E., Isailović, D., Wang, Z., Estrada, J. L., Li, P., & Tector, A. J. (2013) · Xenotransplantation · doi:10.1111/xen.12047 · Cited by 52 · see citing works
Self-citation
Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs
Martens, G. R., Reyes, L. M., Butler, J. R., Ladowski, J. M., Estrada, J. L., Sidner, R. A., Eckhoff, D. E., Tector, M., & Tector, A. J. (2017) · Transplantation · doi:10.1097/tp.0000000000001646 · Cited by 231 · see citing works
Self-citation

Authors: Burlak, C., Paris, L. L., Lutz, A. J., Sidner, R. A., Estrada, J., Li, P., Tector, M., & Tector, A. J.
Affiliations: Indiana University School of Medicine (US)
Indiana University Health (US)
Corresponding author: Tector, A.J.
ORCID: Burlak, C.
Lutz, A.J.
Estrada, J.
Tector, M.
Tector, A.J.
Venue: American Journal of Transplantation
Publisher: Elsevier BV
Published: 2014-08
Volume: 14
Issue: 8
Pages: 1895-1900
ISSN: 1600-6135 (ISSN-L)
DOI: 10.1111/ajt.12744
PMC: PMC4366649
OpenAlex: W1861997829
Cited by: 87
References: 29
Citations by year: 2026: 8 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 12 · 2019: 8 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 9
FWCI: 9.59
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 3036 d)
Locations: American Journal of Transplantation (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
IUScholarWorks (Indiana University) (submittedVersion)
Purdue University Indianapolis (Indiana University) (submittedVersion)
Funders: IU Health Transplant Institute
Topics: Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Keywords: xenotransplantation, genetically modified pigs, GGTA1, CMAH, crossmatch, peripheral blood mononuclear cells, IgM, IgG, chimpanzee comparison, xenogeneic immune response
MeSH terms: Adolescent, Adult, Aged, Animals, Antibodies, Epitopes, Carbohydrates, Pan troglodytes, Female, Galactosyltransferases, Graft Rejection, Humans, Immunoglobulin G, Immunoglobulin M, Leukocytes, Mononuclear, Male, Middle Aged, Protein Binding, Swine, Transplantation, Heterologous, Gene Deletion, Animals, Genetically Modified

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks