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. 2024 May-Jun;31(3):e12862.
doi: 10.1111/xen.12862.

Late graft failure of pig-to-rhesus renal xenografts has features of glomerulopathy and recipients have anti-swine leukocyte antigen class I and class II antibodies

Joseph M Ladowski  1 , Matt Tector  2 , Gregory Martens  3 , Zheng Yu Wang  4 , Chris Burlak  4 , Luz Reyes  4 , Jose Estrada  4 , Andrew Adams  5 , A Joseph Tector  4
Affiliations

Late graft failure of pig-to-rhesus renal xenografts has features of glomerulopathy and recipients have anti-swine leukocyte antigen class I and class II antibodies

Joseph M Ladowski et al. Xenotransplantation. 2024 May-Jun.

Abstract

Prolonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy-largely due to anti-donor MHC antibodies, particularly anti-HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long-surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti-SLA class I and specifically anti-SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti-SLA DQ antibodies. In one recipient tested for anti-SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti-MHC antibodies, particularly anti-SLA DQ, may be a barrier to improved long-term xenograft outcomes.

Keywords: SLA‐DQ; anti‐MHC antibodies; major histocompatibility complex; swine leukocyte antigen; transplant glomerulopathy; xenoantibodies.

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Conflict of interest statement

Financial Conflict of Interest: AJT is founder and equity shareholder of Makana Therapeutics. MT is employed my Makana Therapeutics with share options.

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