Donor‐specific HLA antibodies in paediatric cardiac transplant recipients are associated with poor graft survival

Abstract

There is increasing evidence that DSA are associated with poor graft survival, although there are little data in children. We aimed to describe the incidence of DSA in this group and to determine correlation with graft survival. HLA antibodies were analysed in 59 paediatric cardiac transplant recipients. Mean age 10.4 (0.7-18.5) yr, mean time post-transplant 5.1 (0.3-17.3) yr. Antibody detection/identification was performed on the Luminex platform with subsequent identification using Lifescreen Identification kits/One-Lambda Single antigen kits. Forty patients (69%) had no HLA antibodies. DSA were found in four (7%). One had transient Class I antibodies and normal cardiac function. The other three had persistent Class II antibodies (two subsequently required re-transplantation, the third had cardiac failure due to CAV). Non-DSA were found in 15 (25%), all with normal graft function and without rejection. There was no difference in function or CAV prevalence between those with non-DSA and those without antibodies. HLA DSA is uncommon in paediatric cardiac allograft recipients but, if persistent, suggests poorer prognosis. In our series, antibodies to HLA class II on donor tissue were associated with increased graft loss. Routine screening and regular testing are recommended.

Biopsy-diagnosed antibody-mediated rejection based on the proposed International Society for Heart and Lung Transplantation working formulation is associated with adverse cardiovascular outcomes after pediatric heart transplant

“…[23][24][25][26][27] Likewise, other investigators have found a trend toward younger transplant age and the presence of donor-specific antibodies (DSA) in pediatric HT recipients with a significant association between older donor age and the prevalence of DSA. 28 Future studies on the immunologic changes that occur with age may be important to understanding the pathophysiology of AMR.…”

“…29 -31 Nevertheless, evidence is emerging that circulating DSA in HT recipients is associated with worse graft survival. 28,32 Thus, the coupling of DSA monitoring to biopsy results with grading of AMR may aid in understanding the clinical consequence of the individual test results.…”

Current Concepts in Histocompatibility During Heart Transplant

“…33 Several recent reports have emphasized the clinical effect not only of preformed, but also especially of de novo anti-HLA alloantibodies on graft outcomes in heart transplant recipients. [33][34][35] In particular, de novo anti-HLA donor-specific antibody development was associated with increased rejection, CAV, and poor survival. 30,31,36 Indeed, antibodies against class I or class II antigens seem to have negative effects.…”

Effect of persistent versus transient donor-specific HLA antibodies on graft outcomes in pediatric cardiac transplantation

“…There has been an increase in the number of reports of DSA in pediatric renal 8 and cardiac transplantation, 1,[9][10][11] but there remains little data on the incidence of de novo donor and non-donor-specific HLA antibodies in this group and possible effects on graft outcomes. There have been no longitudinal studies examining the appearance of DSA over the medium and long term in children who have undergone cardiac transplantation.…”