ArticleXenotransplantation
Xenoantibody response to porcine islet cell transplantation using GTKO, CD55, CD59, and fucosyltransferase multiple transgenic donors.
Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.Frontiers in immunology · 2024Review
- The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?Frontiers in endocrinology · 2022Review
- Nanotechnology in Kidney and Islet Transplantation: An Ongoing, Promising Field.Frontiers in immunology · 2022Review
- Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.Xenotransplantation · 2021Article
- Improved production of GTKO/hCD55/hCD59 triple-gene-modified Diannan miniature pigs for xenotransplantation by recloning.Transgenic research · 2020Article
- The role of human CD46 in early xenoislet engraftment in a dual transplant model.Xenotransplantation · 2019Article
- Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?Current diabetes reports · 2018Review
- Generation of GTKO Diannan Miniature Pig Expressing Human Complementary Regulator Proteins hCD55 and hCD59 via T2A Peptide-Based Bicistronic Vectors and SCNT.Molecular biotechnology · 2018Article
- Early barriers to neonatal porcine islet engraftment in a dual transplant model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Article
- Differential Role of B Cells and IL-17 Versus IFN-γ During Early and Late Rejection of Pig Islet Xenografts in Mice.Transplantation · 2017Article
- Pig-to-Primate Islet Xenotransplantation: Past, Present, and Future.Cell transplantation · 2017Review
- Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species.Current transplantation reports · 2017Review
- Optimal pig donor selection in islet xenotransplantation: current status and future perspectives.Journal of Zhejiang University. Science. B · 2014Review
- Rhesus monkeys and baboons develop clotting factor VIII inhibitors in response to porcine endothelial cells or islets.XenotransplantationArticle
- Clonidine inhibits anti-non-Gal IgM xenoantibody elicited in multiple pig-to-primate models.XenotransplantationArticle
- Anti-non-Gal-specific combination treatment with an anti-idiotypic Ab and an inhibitory small molecule mitigates the xenoantibody response.XenotransplantationArticle
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundPromising developments in porcine islet xenotransplantation could resolve the donor pancreas shortage for patients with type 1 diabetes. Using α1,3-galactosyltransferase gene knockout (GTKO) donor pigs with multiple transgenes should extend xenoislet survival via reducing complement activation, thrombus formation, and the requirement for exogenous immune suppression. Studying the xenoantibody response to GTKO/hCD55/hCD59/hHT islets in the pig-to-baboon model, and comparing it with previously analyzed responses, would allow the development of inhibitory reagents capable of targeting conserved idiotypic regions.
methodsWe generated IgM heavy and light chain gene libraries from 10 untreated baboons and three baboons at 28 days following transplantation of GTKO/hCD55/hCD59/hHT pig neonatal islet cell clusters with immunosuppression. Flow cytometry was used to confirm the induction of a xenoantibody response. IgM germline gene usage was compared pre- and post-transplant. Homology modeling was used to compare the structure of xenoantibodies elicited after transplantation of GTKO/hCD55/hCD59/hHT pig islets with those induced by GTKO and wild-type pig endothelial cells without further genetic modification.
resultsIgM xenoantibodies that bind to GTKO pig cells and wild-type pig cells were induced after transplantation. These anti-non-Gal antibodies were encoded by the IGHV3-66*02 (Δ28%) and IGKV1-12*02 (Δ25%) alleles, for the immunoglobulin heavy and light chains, respectively. IGHV3-66 is 86.7% similar to IGHV3-21 which was elicited by rhesus monkeys in response to GTKO endothelial cells. Heavy chain genes most similar to IGHV3-66 were found to utilize the IGHJ4 gene in 85% of V-D regions analyzed. However, unlike the wild-type response, a consensus complementary determining region 3 was not identified.
conclusionsAdditional genetic modifications in transgenic GTKO pigs do not substantially modify the structure of the restricted group of anti-non-Gal xenoantibodies that mediate induced xenoantibody responses with or without immunosuppression. The use of this information to develop new therapeutic agents to target this restricted response will likely be beneficial for long-term islet cell survival and for developing targeted immunosuppressive regimens with less toxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.