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.
Keywords: CAR, cardiac allograft rejection; CD, cluster of differentiation; EMB, endomyocardial biopsy; FoxP3, forkhead box P3; H-score, histology score; IF, immunofluorescence; ISHLT, International Society of Heart and Lung Transplantation; PD-L1, programmed death ligand 1; QmIF, quantitative multiplex immunofluorescence; allograft rejection; immune checkpoint molecules; immune regulation; quantitative immunohistochemistry.
© 2020 The Authors.