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Molecular-level human leukocyte antigen (HLA) mismatch is a powerful biomarker of rejection; however, few studies have explored its use in heart transplant recipients, and none have attempted to use the results of separate algorithms synergistically. Here we tested the hypothesis that a combination of HLAMatchmaker and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) can be used to identify more patients at low risk of rejection.We studied 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC) performing class I and II HLA genotyping by next-generation sequencing to determine eplet mismatch (epMM) load and PIRCHE-II score. Correlation with clinical outcomes was performed on 131 cases.Of the 131 patients, 100 without pre-formed donor specific antibody (DSA) were used to identify cutoffs for the Class I, HLA-DR, and HLA-DQ epMM load and PIRCHE-II score for risk of developing post-transplant DSA (epMM: Class I/DR/DQ = 9/9/6; PIRCHE-II: 141/116/111) and antibody-mediated rejection (ABMR) (epMM: 9/8/8; PIRCHE-II: 157/80/201). Patients with above cut-off epMM load appear to be less likely to develop DSA and ABMR if their PIRCHE-II score is below cut-off (high epMM/high PIRCHE-II: 12.3%-20.3% DSA and 9%-13.5% ABMR vs high epMM/low PIRCHE-II: 4%-10% DSA and 0%-2% ABMR).For the first time in a pediatric heart transplant cohort, immunologic risk cut-offs for DSA and ABMR have been established. When used together, epMM load and PIRCHE-II score allow us to reclassify a portion of cases with high epMM load as having a lower risk for developing DSA and ABMR.

Abiotic factors affect cnidarian-algal symbiosis and, if severe enough, can result in bleaching. Increased temperature and light are well characterized causes of bleaching, but other factors like salinity can also stress the holobiont. In cnidarian-dinoflagellate systems, the expression of host genes, including heat shock protein 70 (Hsp70), changes due to thermal and light stress. In this experiment, we characterized to what extent salinity stress affects Hsp70 expression in the holobiont by simultaneously measuring host and symbiont Hsp70 expression in response to up to 8 h of hypo- and hypersaline conditions in the sea anemone Exaiptasia pallida and its intracellular symbiont Symbiodinium minutum. We show that E. pallida Hsp70 expression increases (6-11-fold) at high salinities whereas Symbiodinium Hsp70 expression shows little change (1.4-2.6-fold). These data suggest that cnidarian Hsp70 response is similar across multiple abiotic stressors further validating the Hsp70 gene as a biomarker for abiotic stress.