Use of an allograft patch in repair of hypoplastic left heart syndrome may complicate future transplantation

Abstract

Objective: Cryopreserved allograft tissue used in the Norwood procedure for infants with hypoplastic left heart syndrome (HLHS) has the potential to cause marked immunologic sensitization which may complicate potential future heart transplantation, if required. The purpose of this study was to assess the anti-HLA antibody response to allograft patches used in the initial repair of HLHS. Methods: A prospective cohort study was conducted comparing the panel-reactive antibody levels (PRA) in 12 infants undergoing repair of HLHS with cryopreserved allograft patch to 10 infants undergoing arterial switch for transposition of the great arteries (no allograft tissue used). PRA for Class I (HLA-A, B, C) and Class II (HLA-DR, DQ) antibodies were assessed preoperatively and postoperatively using flow cytometry. Results: The two groups were well matched at the time of surgery (age, weight, gender). Infants in both groups received blood from multiple donors; however, the allograft group received significantly more (12±10 vs. 5±1 units; P≪0.001). By 4 months, most infants receiving allograft tissue had become highly sensitized for both Class I PRA (62±40 vs. 0; P=0.002) and Class II PRA (49±42 vs. 2±3; P=0.022). This response continued to increase at 12 months: Class I PRA (79±21 vs. 0; P=0.008) and Class II PRA (66±27 vs. 5±6; P=0.008). Specificity analysis confirmed antibodies were specific for the donor allograft HLA type. In addition, infants who were coincidently HLA-matched with their allograft did not develop an elevated PRA. Conclusions: Allograft tissue used in the repair of HLHS is associated with profound donor specific immunologic sensitization in the majority of recipients and may complicate or jeopardize future transplantation. Methods to reduce the immunogenicity of cryopreserved allograft tissue used for arch reconstruction requires further investigation.