*Purpose: Xenotransplantation has been proposed as a bridge to transplant for allosensitized patients. However, the potential of xenotransplantation to broaden HLA allosensitization due to MHC homology has not been explored. Therefore, following pig-kidney xenotransplantation into allosensitized NHP recipients, we evaluated changes in MHC sensitization to SLA, MAMU, and HLA.

*Methods: 5 rhesus macaques were allosensitized with two MHC mismatched NHP donor skin transplantations. They then underwent xenotransplantation with kidneys from genetically modified knockout a-1,3-galactosyltransferase (GGTA1KO) and human decay accelerating factor transgenic (GGTA/CD55Tg) pigs. We evaluated antibody production specifically against their skin donor (allo-MAMU) and pig kidney donor (xeno-SLA) using a flow cytometric crossmatch using cells isolated from skin and kidney donors respectively. Changes in sensitization to HLA were assessed using single antigen bead panels (SAB).

*Results: All 5 allosensitized NHPs showed acute antibody-mediated rejection of the pig-kidneys (MST = 26.8 days). Flow crossmatch tests revealed de novo elevation of xeno-SLA antibodies (Figure A), while allo-mamu antibodies were not increased (Figure B). However, HLA SAB panels showed elevation of HLA-specific antibodies following xenotransplantation in NHP recipients (Figure C). The elevated HLA-specific antibodies were only detected following pig-kidney xenotransplantation and were not present either prior or following NHP allosensitization.

*Conclusions: Xenotransplantation of GGTA/CD55Tg pig-kidneys into 5 NHP allosensitized recipients resulted in de novo MHC antibody production specific to pig (SLA) and human (HLA) but did not promote alloantibody production against their previous NHP donor (MAMU). Further investigation is needed to evaluate SLA and HLA cross-reactivity in xenotransplant recipients.

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