In Situ Immune Profiling of Heart Transplant Biopsies Improves Diagnostic Accuracy and Rejection Risk Stratification
Eliot Peyster, Chichung Wang, Felicia Ishola, Bethany Remeniuk, Clifford Hoyt, Michael D. Feldman, Kenneth B. Margulies
Abstract
Recognizing that guideline-directed histologic grading of endomyocardial biopsy tissue samples for rejection surveillance has limited diagnostic accuracy, quantitative, in situ characterization was performed of several important immune cell types in a retrospective cohort of clinical endomyocardial tissue samples. Differences between cases were identified and were grouped by histologic grade versus clinical rejection trajectory, with significantly increased programmed death ligand 1+, forkhead box P3+, and cluster of differentiation 68+ cells suppressed in clinically evident rejections, especially cases with marked clinical-histologic discordance. Programmed death ligand 1+, forkhead box P3+, and cluster of differentiation 68+ cell proportions are also significantly higher in "never-rejection" when compared with "future-rejection." These findings suggest that in situ immune modulators regulate the severity of cardiac allograft rejection.