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

Background: De novo donor-specific HLA antibodies (DSA) are a risk for poor graft outcomes, but there is little evidence of their long-term effect in pediatric cardiac transplantation or of the effect of transient versus persistent DSA found using newer antibody testing methods.

Methods: Archived serum samples were obtained from patients <18 years of age who underwent primary cardiac transplantation during the period from 1996 to 2009. Luminex antibody testing was performed at 3 months, 6 months and 1 year post-transplant, and then annually. Outcomes including cardiac allograft vasculopathy (CAV), rejection and graft loss were correlated with the presence or absence of DSA or non-donor-specific HLA (non-DSA) antibodies.

Results: Six hundred ninety-one samples from 108 patients, with mean age at transplant of 7.4 (0.1 to 15.9) years and mean follow-up 8.2 (1.9 to 15.7) years, were studied. Forty-three (40%) patients had DSA (which were persistent in 58%), 41 (38%) had non-DSA (persistent in 46%) and 24 (22%) had no antibodies. In those with DSA, 30% had Class I antibodies, 47% Class II and 23% both Class I and II, whereas, in the subgroup with persistent DSA, 88% had Class II antibodies. There were 14 cases of graft loss, 9 of these in patients with persistent DSA. All had Class II antibodies. There was an increased incidence of CAV, rejection and graft loss in those with persistent DSA. Outcomes were similar between the group with non-DSA antibodies and the group with no antibodies.

Conclusions: De novo HLA antibodies are detectable post-transplant in the majority of patients, but non-DSA and transient DSA do not appear to be associated with poor outcomes. Patients with persistent DSA, especially those with Class II DQ antibodies, have worse survival.