A-Antigen (Ag)-Specific Tolerance Following A-Ag Administration to Infant Mice.
1Dept Pediatrics, Alberta Transplant Institute, Canadian National Transplant Research Program, University of Alberta, Edmonton, Canada
2Dept Chemistry, Alberta Glycomics Centre, University of Alberta, Edmonton, Canada
3Immunology Research Centre, St Vincent's Hospital, University of Melbourne, Melbourne, Australia
Meeting: 2017 American Transplant Congress
Abstract number: C269
Keywords: Antibodies, Heart, Mice, Tolerance
Session Information
Session Name: Poster Session C: Tolerance/Immune Regulation
Session Type: Poster Session
Date: Monday, May 1, 2017
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 November 21, 2024.« Back to 2017 American Transplant Congress