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Sensitization via Pregnancy Generates Alloantibody and Cross-Reactive Xeno-Antibody in a Non-Human Primate Model

J. Yoon, M. Manook, Z. Fitch, R. Schmitz, A. Choi, A. M. Jackson, S. Knechtle, J. Kwun

Surgery, Duke University, Durham, NC

Meeting: 2020 American Transplant Congress

Abstract number: A-278

Keywords: Alloantibodies, Pregnancy, Sensitization, Xenoreactive antibodies

Session Information

Session Name: Poster Session A: Xenotransplantation

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*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).

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*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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To cite this abstract in AMA style:

Yoon J, Manook M, Fitch Z, Schmitz R, Choi A, Jackson AM, Knechtle S, Kwun J. Sensitization via Pregnancy Generates Alloantibody and Cross-Reactive Xeno-Antibody in a Non-Human Primate Model [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/sensitization-via-pregnancy-generates-alloantibody-and-cross-reactive-xeno-antibody-in-a-non-human-primate-model/. Accessed May 10, 2025.

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