Abstract 12748: Tolerance in the Setting of Pediatric ABO-Incompatible Heart Transplantation: Is B-cell Elimination the Sole Mechanism?
Graft acceptance following ABO-Incompatible (ABO-I) heart transplants (HTx) in the pediatric population has been associated with a lack of B-cells that produce donor specific blood group isohemagglutinins (ISOs). However, there have been recent reports of detectable donor specific ISOs. The objectives of this study were to describe the pattern of and risk factors for development of donor specific ISOs, and to determine their effects on rejection and survival following ABO-I HTx. Children who underwent an ABO-I HTx (1992-2009) were included. ISO titers post-HTx and clinical outcomes were reviewed. Logistic regression, adjusted for duration of follow-up, identified factors associated with the development of donor specific ISO titers ≥1:8. Twenty seven percent of patients (n=11/41) produced donor specific ISOs. Anti-A was more commonly produced in at risk patients in comparison to Anti-B (39% vs. 8%; p=0.04; Figure). The median time to peak Anti-A titer was 1.2y (0.1-6.5y) and for Anti-B was 0.5y (0.1-0.9y). Factors associated with the development of donor specific ISOs included: older age at HTx (Odds Ratio:1.2/month, p=0.05), pre-HTx Anti-B level ≥1:8 (OR:25.0,p=0.07), and pre-HTx HLA sensitization (OR:5.0,p=0.08). Older age at HTx (OR: 2.3/month, p=0.06) and pre-HTx HLA sensitization (OR:22.4, p=0.04) were also associated with Anti-A production. The presence of donor specific ISOs did not increase the risk of antibody-mediated rejection, frequency of cellular rejection or death, but were associated with a higher maximum grade of cellular rejection (OR 3.9, 95% CI:0.88-17.28, p=0.07). Donor specific isohemagglutinins develop in one-third of patients following ABO-I HTx. Production of these antibodies appears to differ depending on the donor blood group. The presence of these antibodies has little impact on clinical outcomes but does suggest that mechanisms other than B-cell elimination may be responsible for graft acceptance in this cohort of patients.
- © 2010 by American Heart Association, Inc.