ArticleXenotransplantation
Minimal effect of bortezomib in reducing anti-pig antibodies in human leukocyte antigen-sensitized patients: a pilot study.
Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Genetically engineered porcine liver: a new era in transplantation.International journal of surgery (London, England) · 2026Article
- The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Xenotransplantation tolerance: applications for recent advances in modified swine.Current opinion in organ transplantation · 2018Review
- Xenotransplantation: immunological hurdles and progress toward tolerance.Immunological reviews · 2014Review
- Desensitization With Proteasome Inhibition and Costimulation Blockade Modulates the Xenoreactive Humoral Response in Nonhuman Primate Xenotransplantation.XenotransplantationArticle
- Antibody-mediated rejection in xenotransplantation: Can it be prevented or reversed?XenotransplantationReview
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundBortezomib, a proteasome inhibitor used to treat multiple myeloma, has been administered (± plasma exchange ± intravenous immunoglobulin [IVIg]) in attempts to reduce antibodies against human leukocyte antigens (HLA) in sensitized patients undergoing organ transplantation. To our knowledge, bortezomib has not been investigated for its effect on natural anti-pig antibodies. If bortezomib could reduce the production of anti-pig antibodies, this would likely be beneficial to the outcome of pig organ grafts in primates.
methodsNine patients received bortezomib either to reduce anti-HLA antibody levels before organ allotransplantation or to treat antibody-mediated rejection. Patients at the Mayo Clinic (Group 1; n = 4) received bortezomib alone, whereas at the UPMC (Group 2; n = 5), this was combined with plasmaphereses ± IVIg in some cases. Anti-pig IgM and IgG levels against wild-type (WT) and α1,3-galactosyltransferase gene knockout (GTKO) pig aortic endothelial cells (flow cytometry-relative mean fluorescence intensity) and anti-Gal IgM and IgG (ELISA-OD480 nm ) were measured pre- and post-bortezomib therapy.
resultsMean anti-pig IgM levels were 11.2 (WT) and 1.9 (GTKO) pre-bortezomib treatment and 9.4 (WT: P = 0.02) and 1.7 (GTKO: P = 0.33) post-bortezomib treatment, respectively. Mean anti-pig IgG levels were 4.3 (WT) and 1.5 (GTKO) pre-bortezomib treatment and 3.6 (WT: P = 0.21) and 1.4 (GTKO: P = 0.20) post-bortezomib treatment, respectively. Mean anti-Gal IgM and IgG levels were 0.7 and 1.1, respectively, pre-treatment, and 0.6 (P = 0.03) and 1.1 (NS), respectively, post-treatment. When the data were analyzed in Groups 1 and 2 separately, there were no significant differences between the pre- and post-bortezomib levels of anti-pig, anti-non-Gal, or anti-Gal IgM or IgG.
conclusionsFrom this limited study, we conclude that bortezomib might reduce anti-Gal IgM levels in primates, but, in this respect alone, is unlikely to have any significant effect on the outcome of GTKO pig organ transplantation.
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