Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose: In contrast to adults, ABO-incompatible heart transplantation (ABOi HTx) can safely be performed in infants due to absent/low levels of anti-A/B antibodies (Ab). Tolerance develops to donor blood group A/B-Ag after ABOi HTx by mechanisms not well-defined. Using a novel A-transgenic (A-Tg; C57BL/6, B6) mouse model we showed A-Ag specific tolerance following HTx into young (4 weeks old) wild-type B6 (WT) mice. Herein, we explored tolerance induction to A-Ag in a form other than a transplant. A-Tg erythrocytes (RBC) express A-Ag at high levels. We hypothesized that treatment of infant WT mice (≤3 weeks old) with A-Tg RBC would induce A-Ag specific tolerance, allowing subsequent ABOi HTx.
Methods: WT mice were injected i.p. at age 7, 14, and 21 days with: 1) intact A-Tg RBC; 2) A-Tg RBC membranes; 3) human A RBC membranes (hA-RBCs); or 4) left untreated (Table). As adults (7 weeks), all mice were injected i.p. (weekly x4) with hA-RBC in an attempt to elicit anti-A Ab. Serum anti-A and 3rd-party (non-A anti-human RBC) Ab were assessed by hemagglutination/ELISA.
Results: Following A-sensitization, high levels of anti-A Ab developed in untreated mice and mice neonatally-treated with hA-RBCs or A-Tg RBC membranes (Table). In contrast, anti-A remained absent/low in A-sensitized mice treated as neonates with intact A-Tg RBC (Table); 3rd-party Ab levels were high in all (median titre 1:64).Conclusions: The inability to elicit anti-A Ab in A-sensitized adult mice neonatally-treated with intact A-Tg RBCs, together with abundant production of 3rd-party Ab, suggests development of robust A-Ag specific tolerance. Our findings suggest that the form of A-Ag (intact cells vs membrane), that may relate to antigen persistence, is critical to B cell tolerance in this setting. Intentional induction of tolerance to A/B-antigen(s) in infancy may allow later ABOi HTx.
CITATION INFORMATION: Motyka B, Wang Y, Lamarche B, Adam I, Pearcey J, Tao K, Cairo C, Cowan P, West L. A-Antigen (Ag)-Specific Tolerance Following A-Ag Administration to Infant Mice. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Motyka B, Wang Y, Lamarche B, Adam I, Pearcey J, Tao K, Cairo C, Cowan P, West L. A-Antigen (Ag)-Specific Tolerance Following A-Ag Administration to Infant Mice. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/a-antigen-ag-specific-tolerance-following-a-ag-administration-to-infant-mice/. Accessed February 26, 2021.
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