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Allosensitization and outcomes in pediatric heart transplantation
William T Mahle1, Margaret A Tresler, R Erik Edens
1Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA. wmahle@emory.edu
Insights
High panel-reactive antibody (PRA) levels in pediatric heart transplant candidates increase waitlist mortality and decrease post-transplant survival. Negative prospective crossmatches mitigate this risk, highlighting the need for desensitization strategies.
Area of Science:
- Pediatric Cardiology
- Transplantation Immunology
- Immunosuppression
Background:
- Allosensitization, indicated by elevated panel-reactive antibody (PRA) titers, presents a significant challenge in pediatric heart transplantation.
- The optimal management strategy for pediatric heart transplant candidates with high PRA remains a subject of debate.
Purpose of the Study:
- To investigate the association between elevated PRA levels and outcomes in pediatric heart transplant recipients.
- To evaluate the impact of PRA on waitlist mortality and post-transplant survival.
Main Methods:
- Analysis of data from 3,016 pediatric patients listed for heart transplantation between 1993 and 2008.
- Inclusion of PRA data at listing and at the time of transplantation, using the highest reported value regardless of assay methodology.
- Comparison of outcomes between patients with high PRA (≥50%) and low PRA (<10%).
Main Results:
- Elevated PRA at listing was associated with a higher risk of death while awaiting transplantation.
- Patients with PRA ≥50% had lower transplant rates (57% vs. 76% within 1 year) and higher 12-month waitlist mortality (19%) compared to those with PRA <10%.
- One-year post-transplant survival was significantly lower for patients with PRA ≥50% (73%) versus PRA <10% (90%). Negative prospective crossmatches eliminated this survival disparity.
Conclusions:
- Significant allosensitization doubles the risk of death within the first year post-transplant.
- Prospective crossmatching can prevent post-transplant mortality but may increase pre-transplant attrition due to longer wait times.
- There is an urgent need for strategies to reduce the impact of allosensitization and antibody-mediated rejection in pediatric heart transplantation.
Background:
Allosensitization among children being considered for heart transplantation remains a great challenge. Controversy exists as to the best approach for those with elevated panel-reactive antibody (PRA) titers. We sought to define the association between elevated PRA and outcomes using data from the multi-institutional Pediatric Heart Transplant Study Group.
Methods:
Between January 1993 and December 2008, 3,016 patients (>1 month of age) were listed for heart transplantation. PRA data at listing were available for 2,500 (83%) patients, and 2,237 underwent transplantation with PRA data being available for 1,904 (85%). Because various PRA assays were employed (e.g., cell-based and solid phase) we entered the highest value regardless of methodology.
Results:
Among the factors associated with high PRA at transplant were Status 1 at listing, previous sternotomy and prior Norwood procedure. An elevated PRA at listing was associated with higher risk of death while waiting. Of subjects with PRA ≥ 50% only 57% were transplanted by 1 year on the waitlist, as compared with 76% of those with PRA <10%. Waitlist mortality for the highly allosensitized subjects (≥ PRA 50%) was 19% by 12 months. Survival at 1 year after transplantation was significantly lower in those with PRA ≥ 50% versus those with PRA <10% (73% vs 90%, respectively, p < 0.0001). Those with elevated PRA who had a negative prospective crossmatch had no difference in survival compared with those without allosensitization. There was no significant association between PRA levels and time to first rejection or development of coronary allograft vasculopathy.
Conclusions:
Significant allosensitization is associated with more than a 2-fold increased risk of death within the first transplant year. Although prospective crossmatching abrogates the risk of post-transplant mortality, it may contribute to higher pre-transplant attrition due to longer waitlist times. There is a critical need for strategies to minimize the impact of allosensitization and antibody-mediated rejection immediately after transplantation.
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