Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: ABO-incompatible heart transplantation (ABOi HTx) is safe in young children and increases donor access. Post-ABOi HTx, B cell tolerance develops to donor ABO blood group antigen(s) by mechanisms not fully defined. To study ABO tolerance, we developed A-transgenic mice (A-Tg) that express A-antigen on vascular endothelium, erythrocytes (RBCs) and lymphocytes; we demonstrated A-antigen-specific tolerance induced by HTx into 4-week-old, MHC-identical, wild-type mice. Intentional induction of tolerance may allow subsequent ABOi HTx. Recently, we showed ABO tolerance could be intentionally induced in wild-type mice after intraperitoneal (ip) injection of infant mice with intact A-Tg blood cells (BCs). Herein, we sought to determine specific A-Tg cell type(s) capable of inducing tolerance.
*Methods: Wild-type BALB/c (BALB) mice at 7 days of age were left untreated or injected ip (weekly×3) with either unfractionated BCs, RBCs, peripheral blood mononuclear cells (PBMCs), or splenocytes from A-Tg BALB mice (see Table). Two weeks later, all mice were injected ip (weekly×5) with human A-RBC (A-antigen challenge) in an attempt to elicit anti-A antibody production. Serum anti-A and third-party (non-A anti-human) antibody were assessed by hemagglutination or ABH glycan microarray.
*Results: In response to challenge with A-antigen, high levels of anti-A antibody were produced both in untreated mice and in mice previously treated with A-Tg PBMCs or splenocytes (Table). In contrast, anti-A antibody remained undetectable/very low in mice treated as infants with A-Tg BCs or RBCs. Third-party antibody responses were high for all groups.
*Conclusions: A-Tg RBCs induced robust A-antigen-specific tolerance in infant mice, whereas A-Tg lymphocytes (PBMCs, splenocytes) did not. Future studies will explore mechanisms of A-Tg RBC tolerance induction with the goal to design synthetic ABH-multivalent polyethylene glycol (PEG) glycoconjugates for intentional ABO tolerance to allow subsequent ABOi HTx safely.
To cite this abstract in AMA style:Motyka B, Fersovich J, Sulzer M, Adam I, Pearcey J, Tao K, Cairo CW, Cowan PJ, West LJ. Tolerance to ABO A-Antigen Following Treatment of Infant Mice with A-Expressing MHC-Identical Erythrocytes [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/tolerance-to-abo-a-antigen-following-treatment-of-infant-mice-with-a-expressing-mhc-identical-erythrocytes/. Accessed December 9, 2019.
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