Development of donor-specific isohemagglutinins following pediatric ABO-incompatible heart transplantation

Graft acceptance following pediatric ABO-incompatible heart transplantation has been associated with a deficiency of donor-specific isohemagglutinins (DSI) due to B-cell elimination. Recent observations suggest that some of these patients do produce DSI. The purpose of this study was to examine the pattern of, risk factors for development and clinical impact of DSI. All children who underwent an ABO-incompatible heart transplant (1996-2009) were included. Serial postheart transplantation DSI titers and clinical outcomes were reviewed. DSI were produced in 27% of the patients (n = 11/41). Anti-A production was significantly greater in "at risk" patients than Anti-B (39% vs. 8%; p = 0.04). Risk factors associated with the development of DSI included: older age at transplantation (HR: 1.15/month, p = 0.04), pretransplant Anti-B level ≥ 1:8 (HR: 9.61, p = 0.004) and HLA sensitization (HR: 2.80, p = 0.11). The presence of DSI did increase the risk of cellular rejection but not antibody-mediated rejection, allograft vasculopathy, graft loss or death. Although these antibodies do not result in any significant clinical consequences, their presence suggests that B-cell tolerance is not the sole mechanism of graft acceptance.