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This is an observational study with the primary objective to measure donor-specific immune responses by pediatric liver transplant (LT) recipients, using cell surface expression of lymphocyte activation markers and cytokine secretion in mixed lymphocyte reactions. The secondary objective was to demonstrate possible mechanism(s) involved in those who demonstrated donor-specific hyporesponsiveness. Study participants included 17 recipients, their respective parental donors, the non-donor parent, as well as unrelated third party individuals. Within the CD4(+) population, two distinct patterns of CD69 and CD71 expressions were observed: recipients who had a lower percentage of CD4(+)CD69(+) and CD4(+)CD71(+) cells after donor versus non-donor stimulation (therefore a donor/non-donor ratio1); and recipients who had a higher percentage of CD4(+)CD69(+) and CD4(+)CD71(+) cells after donor versus non-donor stimulation (therefore a donor/non-donor ratio ≥1). Eight recipients had the above defined ratio of1, with significantly decreased interferon-γ secretion after donor versus non-donor stimulation. CD4(+)CD25(hi.)CD127- regulatory T cells from these eight recipients suppressed donor and non-donor cell induced proliferation. Suppression of proliferation was partially abrogated by interleukin-2. In conclusion, CD69 and CD71 cell surface expression with interferon-γ secretion can be used to identify two distinct populations in pediatric LT recipients. Both active regulation and anergy underlie donor specific hyporesponsiveness.

Aim The significance of HLA antibody in liver transplantation has been unclear, although recent studies have described an increase in the diagnosis of antibody mediated damage in this population. Our specific aim is to correlate the development of de novo HLA antibody including C1q testing, and AT1R antibody levels with graft dysfunction to determine if there is a significant association of these antibodies with graft function. Methods 63 patients at our center from 7/31/1998 to 2/29/16 were included for analysis, of which 42 were screened for Anti-HLA DSA, C1q and AT1R. DSA >1000 mfi was considered positive and patients were evaluated retrospectively for ACR. Specificity of antibody locus as well as alleles were analyzed and correlated with liver dysfunction. Available biopsies were evaluated for rejection grade, mean fibrosis score as well as portal, central, and sinusoidal fibrosis. Patient characteristics were summarized using mean, standard deviation, median and range for continuous variable, frequency and percentage for categorical variable. Wilcoxon Rank Sum or Kruskal Wallace test was conducted to check differences of continuous variables. Two sided p value less than 0.05 was considered as statistically significant. Results Portal fibrosis scores were significantly lower in patients without Class II DQ DSA post transplant ( p p p p Conclusions There is significant development of Class II DSA in pediatric liver transplantation. These antibodies were associated with increases in fibrosis scoring and ACR. DQ2 mismatches in particular were shown to be more immunogenic, the significance of which is currently under study.