Humoral rejection in pediatric orthotopic heart transplantation

Pediatric heart transplant grafts may fail without evidence of cellular rejection or transplant coronary artery disease. The role of antibody-mediated humoral rejection (HR) in graft failure has not yet been described in the pediatric population.

We reviewed the medical records of 103 pediatric heart transplantations performed at our institution from July 1997 to June 2004. Biopsy specimens were evaluated for HR histologically and by immunoperoxidase and immunofluorescence staining. Risk factors for HR were determined by statistical analysis. Graft survival curves were constructed and compared for patients testing negative or positive for HR.

A total of 358 endomyocardial biopsies (EMBs) from 103 pediatric heart transplant patients (age 3 weeks to 20 years; 52% males) were analyzed for HR. Thirty-six grafts (32%) showed evidence of HR. Grafts with a history of HR during the first year after transplant had a 47% failure rate over 3 years, compared with 29% of those hearts with no evidence of HR (p = 0.06). Although patients with congenital heart disease (CHD) appeared to be at greatest risk for developing HR (p = 0.01), patients with positive donor-specific crossmatch data showed a trend toward more significant risks for HR (p = 0.055). Hemodynamic data (including pulmonary capillary wedge pressure [PCWP] and cardiac index [CI]), left ventricular ejection fraction (LVEF), gender matching, recipient age, race of recipient vs donor and pre-transplant panel-reactive antibody (PRA) were not predictive of HR.

Patients with a pathologic diagnosis of HR have increased graft failure rates and overall mortality. Patients with congenital heart disease and positive cross-match results may be at increased risk for HR.