Academic Journal
Xenotransplant Histocompatibility Assays: Improving Detection of Antibodies Which Bind Class II Swine Leukocyte Antigens While Avoiding Artifacts.
| Τίτλος: | Xenotransplant Histocompatibility Assays: Improving Detection of Antibodies Which Bind Class II Swine Leukocyte Antigens While Avoiding Artifacts. |
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| Συγγραφείς: | Tector M; Makana Therapeutics, Miami, FL., Wang ZY; Department of Surgery, University of Miami School of Medicine, Miami, FL., Copsel S; Makana Therapeutics, Miami, FL., Ray B; Werfen, Barcelona, Spain., Hariharan J; Werfen, Barcelona, Spain., Haver H; Werfen, Barcelona, Spain., Estrada JL; Department of Surgery, University of Miami School of Medicine, Miami, FL., Reyes LM; Department of Surgery, University of Miami School of Medicine, Miami, FL., Gennuso VN; Department of Surgery, University of Miami School of Medicine, Miami, FL., Figueroa O; Department of Surgery, University of Miami School of Medicine, Miami, FL., Vianna RM; Department of Surgery, University of Miami School of Medicine, Miami, FL., Tector AJ; Department of Surgery, University of Miami School of Medicine, Miami, FL.; Founder Makana Therapeutics, Miami, FL. |
| Πηγή: | Transplantation [Transplantation] 2026 May 01; Vol. 110 (5), pp. e988-e998. Date of Electronic Publication: 2026 Feb 17. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0132144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1534-6080 (Electronic) Linking ISSN: 00411337 NLM ISO Abbreviation: Transplantation Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hagerstown, MD : Lippincott Williams & Wilkins Original Publication: Baltimore, Williams & Wilkins. |
| Ιατρικοί όροι (MeSH): | Histocompatibility Antigens Class II*/immunology , Leukocytes, Mononuclear*/immunology , Histocompatibility Testing*/methods , Histocompatibility Antigens Class I*/immunology , Antibodies, Heterophile*/immunology , Isoantibodies*/immunology , Isoantibodies*/blood, Endothelial Cells/immunology ; Endothelial Cells/metabolism ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Kidney/immunology ; Kidney/cytology ; Animals ; Transplantation, Heterologous ; Humans ; Swine ; Immunity, Humoral ; Kidney Transplantation ; Cells, Cultured |
| Περίληψη: | Background: Human xenotransplantation has begun, but antibody-mediated rejection remains a major barrier to success despite reducing donor xenoantigenicity through genetic engineering. Consequently, as in allotransplantation potential recipients must be carefully tested to determine whether they have pre-formed anti-pig antibodies. These antibodies target glycans and major histocompatibility complex proteins, known as swine leukocyte antigens (SLA). Predicting donor-specific humoral immunity remains challenging because the xenotransplant histocompatibility assays are in early phases of development. Methods: We studied the binding of human antibodies to porcine peripheral blood mononuclear cells (PBMCs) and renal endothelial cells. We examined whether in vitro conditions affected the detection of antibodies by the endothelial cells. We also tested these cells' ability to detect antibodies to class II SLA proteins. Finally, we studied whether beads, coated with SLA proteins, enabled anti-SLA immunoglobulin to be identified. Results: Renal endothelial cells can benefit from and suffer from in vitro manipulations. These cells can be made to express class II SLA proteins increasing their ability to detect anti-pig antibodies. However, endothelial cells also acquire Neu5Gc from the environment when in culture which increases background signal as anti-Neu5Gc antibodies bind these targets. Although not experiencing in vitro acquisition of xenoantigens, PBMC struggled to detect IgG and IgM toward class II SLA proteins. Beads, coated with individual class II SLA proteins, did detect anti-pig IgG and IgM that was missed by the PBMC. Conclusions: Our findings suggest that complementary assays may be essential to reliably identify xenotransplant candidates at minimal risk of antibody-mediated rejection. (Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.) |
| Competing Interests: | A.J.T. is a founder and shareholder in Makana Therapeutics. M.T. is the Chief Scientific Officer and has options in Makana Therapeutics. B.R. is a Senior Director at Werfen. J.H. is a senior manager of Werfen. H.H. is a research associate at Werfen. S.C. is a senior scientist and holds options at Makana Therapeutics. The other authors declare no conflicts of interest. |
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| Grant Information: | NIH NIAID U19 AI142737 makana therapeutics, Werfen |
| Substance Nomenclature: | 0 (swine leukocyte antigen) 0 (Histocompatibility Antigens Class II) 0 (Histocompatibility Antigens Class I) 0 (Antibodies, Heterophile) 0 (Isoantibodies) |
| Entry Date(s): | Date Created: 20260217 Date Completed: 20260707 Latest Revision: 20260707 |
| Update Code: | 20260708 |
| DOI: | 10.1097/TP.0000000000005651 |
| PMID: | 41700989 |
| Βάση Δεδομένων: | MEDLINE |
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