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In Situ Immune Profiling of Heart Transplant Biopsies Improves Diagnostic Accuracy and Rejection Risk Stratification

Authors: Peyster, Eliot G.; Wang, Chichung; Ishola, Felicia; Remeniuk, Bethany; Hoyt, Clifford; Feldman, Michael D.; Margulies, Kenneth B.

Online: https://linkinghub.elsevier.com/retrieve/pii/S2452-302X(20)30062-0

Issue: JACC Basic Transl Sci. 2020 Apr 1;5(4):328-340.


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.