CoChat
Sign Up
Cited by 125

The DOI matches its Crossref record.

Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation

Adams, Andrew B., Lovasik, Brendan P., Faber, David A., Burlak, Christopher, Breeden, Cynthia, Estrada, Jose L., Reyes, Luz M., Vianna, Rodrigo M., Tector, Matthew F., Tector, Alfred J.·2021·Annals of Surgery
DOI 10.1097/sla.0000000000004996PMC PMC8915445
Open this paper in CoChat — free account

Abstract

Objective: Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression. Methods: Double (Gal and Sd a ) and triple xenoantigen (Gal, Sd a , and SLA I) pigs were created using CRISPR/Cas. Kidneys from DKO and TKO pigs were transplanted into rhesus monkeys that had the least reactive crossmatches. Recipients received anti-C5 antibody weekly for 70 days, and T cell depletion, anti-CD154, mycophenolic acid, and steroids as baseline immunosuppression (n = 7). Control recipients did not receive anti-C5 therapy (n = 10). Results: Temporary anti-C5 therapy reduced early graft loss secondary to antibody-mediated rejection and improved graft survival ( P < 0.01). Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody-mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62 days. Conclusion: Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.

Overview

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1097/sla.0000000000004996

Cites

Statistics

Verification

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

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

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

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 32

  1. Chen, 2005, Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys, Nat Med, 11, 1295, 10.1038/nm1330 · DOI
  2. Higginbotham, 2015, Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model, Xenotransplantation, 22, 221, 10.1111/xen.12166 · DOI
  3. Dorling, 2003, Are anti-endothelial cell antibodies a pre-requisite for the acute vascular rejection of xenografts?, Xenotransplantation, 10, 16, 10.1034/j.1399-3089.2003.01134.x · DOI
  4. Cowan, 2017, Reducing the threshold for clinical renal xenotransplantation, Transplantation, 101, 692, 10.1097/TP.0000000000001641 · DOI
  5. Estrada, 2015, Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/beta4GalNT2 genes, Xenotransplantation, 22, 194, 10.1111/xen.12161 · DOI · Paper page
  6. Martens, 2017, Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs, Transplantation, 101, e86, 10.1097/TP.0000000000001646 · DOI
  7. Adams, 2018, Xenoantigen Deletion and Chemical Immunosuppression Can Prolong Renal Xenograft Survival, Ann Surg, 268, 564, 10.1097/SLA.0000000000002977 · DOI
  8. Kim, 2019, Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion, Am J Transplant, 19, 2174, 10.1111/ajt.15329 · DOI · Paper page
  9. McGregor, 2012, Human CD55 expression blocks hyperacute rejection and restricts complement activation in Gal knockout cardiac xenografts, Transplantation, 93, 686, 10.1097/TP.0b013e3182472850 · DOI
  10. Cui, 2020, Evidence for GTKO/beta4GalNT2KO pigs as the preferred organ-source for old world nonhuman primates as a preclinical model of xenotransplantation, Transplant Direct, 6, e590, 10.1097/TXD.0000000000001038 · DOI
  11. Yamamoto, 2020, Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout), Sci Rep, 10, 9771, 10.1038/s41598-020-66311-3 · DOI · Paper page
  12. Park, 2019, Induction of accommodation by anti-complement component 5 antibody-based immunosuppression in ABO-incompatible heart transplantation, Transplantation, 103, e248, 10.1097/TP.0000000000002808 · DOI
  13. Marks, 2019, Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: a randomized trial, Am J Transplant, 19, 2876, 10.1111/ajt.15364 · DOI
  14. Brachet, 2016, Eculizumab epitope on complement C5: progress towards a better understanding of the mechanism of action, Mol Immunol, 77, 126, 10.1016/j.molimm.2016.07.016 · DOI
  15. Li, 2015, Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection, Xenotransplantation, 22, 20, 10.1111/xen.12131 · DOI
  16. Reyes, 2014, Creating class I MHC-null pigs using guide RNA and the Cas9 endonuclease, J Immunol, 193, 5751, 10.4049/jimmunol.1402059 · DOI
  17. Montgomery, 2011, Humoral immunity and antibody-mediated rejection in solid organ transplantation, Semin Immunol, 23, 224, 10.1016/j.smim.2011.08.021 · DOI
  18. Jordan, 2020, Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients: results of an international phase 2 trial (Highdes), Transplantation
  19. Lonze, 2018, IdeS (Imlifidase): a novel agent that cleaves human igg and permits successful kidney transplantation across high-strength donor-specific antibody, Ann Surg, 268, 488, 10.1097/SLA.0000000000002924 · DOI
  20. Murase, 1993, Hamster-to-rat heart and liver xenotransplantation with FK506 plus antiproliferative drugs, Transplantation, 55, 701, 10.1097/00007890-199304000-00003 · DOI
  21. Langer, 1993, Humoral and cellular immunopathology of hepatic and cardiac hamster-into-rat xenograft rejection. Marked stimulation of IgM++bright/IgD+dull splenic B cells, Am J Pathol, 143, 85
  22. Lin, 1998, Induction of specific transplantation tolerance across xenogeneic barriers in the T-independent immune compartment, Nat Med, 4, 173, 10.1038/nm0298-173 · DOI
  23. Chong, 2000, Tolerance of T-independent xeno-antibody responses in the hamster-to-rat xenotransplantation model is species-restricted but not tissue-specific, Xenotransplantation, 7, 48, 10.1034/j.1399-3089.2000.00037.x · DOI
  24. Li, 2007, Rapidly induced, T-cell independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells, Blood, 110, 3926, 10.1182/blood-2007-01-065482 · DOI
  25. Volz, 2015, Antibody therapies and their challenges in the treatment of age-related macular degeneration, Eur J Pharm Biopharm, 95, 158, 10.1016/j.ejpb.2015.02.020 · DOI
  26. Jordan, 2020, Intravenous immunoglobulin significantly reduces exposure of concomitantly administered anti-C5 monoclonal antibody tesidolumab, Am J Transplant, 20, 2581, 10.1111/ajt.15922 · DOI
  27. Mohiuddin, 2014, One-year heterotopic cardiac xenograft survival in a pig to baboon model, Am J Transplant, 14, 488, 10.1111/ajt.12562 · DOI
  28. Langin, 2018, Consistent success in life-supporting porcine cardiac xenotransplantation, Nature, 564, 430, 10.1038/s41586-018-0765-z · DOI
  29. Spicer, 2019, Costimulatory pathway targets for autoimmune and inflammatory conditions: clinical successes, failures, and hope for the future, Expert Opin Investig Drugs, 28, 99, 10.1080/13543784.2019.1557146 · DOI
  30. Martens, 2019, HLA class I-sensitized renal transplant patients have antibody binding to SLA class I epitopes, Transplantation, 103, 1620, 10.1097/TP.0000000000002739 · DOI
  31. Koenig, 2021, Missing self-induced activation of NK cells combines with non-complement-fixing donor-specific antibodies to accelerate kidney transplant loss in chronic antibody-mediated rejection, J Am Soc Nephrol, 32, 479, 10.1681/ASN.2020040433 · DOI
  32. Puga Yung, 2017, The Role of NK cells in pig-to-human xenotransplantation, J Immunol Res, 2017, 4627384, 10.1155/2017/4627384 · DOI

Cited by

Sorted by citations

Metadata

Authors
Adams, A. B., Lovasik, B. P., Faber, D. A., Burlak, C., Breeden, C., Estrada, J. L., Reyes, L. M., Vianna, R. M., Tector, M. F., & Tector, A. J.
Venue
Annals of Surgery
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-07-07
Volume
274
Issue
3
Pages
473-480
ISSN
  • 0003-4932
  • 1528-1140
DOI
10.1097/sla.0000000000004996
PMC
PMC8915445
Cited by
125
References
0
Language
en

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