*Purpose: Women are disproportionately represented among highly sensitized waitlist candidates and within HLA-incompatible transplantation programs. Due to difficulties obtaining compatible donors, sensitized patients are seen as potential first-in-human recipients of xenotransplantation. Use of Gal-Knockout (GKO) porcine donors have reduced rejection risk in xenotransplantation; however, efficacy in the context of HLA sensitization, including sensitization via pregnancy,needs further study. In a preclinical non-human primate model, we sought to examine the effect of pregnancy in multiparous recipients on humoral incompatibility to allografts and xenografts.

*Methods: We tested plasma from 10 multiparous female and 10 naïve male rhesus macaques for allo- and xeno-reactive antibodies using 10 NHP donors and 2 porcine donors (wild type [WT] and Gal-Knockout [GKO]) in flow cytometric T and B cell (not shown) crossmatch tests. We report T-cell cross match (class I) values as normalized ratios (fold increased to no plasma control).

*Results: Multiparous female monkeys demonstrate greater class I and II reactivity against a range of potential NHP donors, compared to male monkeys (Figure A). In addition, compared to male monkeys, multiparous femaless demonstrated greater cross reactivity against cells from WT pig donors (p<0.05). Interestingly, these multiparous females showed higher preformed antibody level against GKO donor cells compared to male monkeys (p<0.01). (Figure B).

*Conclusions: Multiparous female monkeys demonstrate increased humoral immunity against potential allo and xeno-donors. Humoral risk for multiparous females was not diminished by the lack of a-1,3-galactosyltransferase in GKO pig donors. Xenotransplantation offers difficult to transplant patients greater access to organs, however, multiparous females may not benefit from this new transplant modality.

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