Author + information
- Received December 15, 2019
- Revision received January 24, 2020
- Accepted January 24, 2020
- Published online April 27, 2020.
- Eliot G. Peyster, MDa,
- Chichung Wang, MSb,
- Felicia Ishola, BSb,
- Bethany Remeniuk, PhDb,
- Clifford Hoyt, MSb,
- Michael D. Feldman, MD, PhDc and
- Kenneth B. Margulies, MDa,∗ ()
- aCardiovascular Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania
- bAkoya Biosciences, Hopkinton, Massachusetts
- cDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- ↵∗Address for correspondence:
Dr. Kenneth B. Margulies, Perelman School of Medicine, University of Pennsylvania, Translational Research Center, Room 11–101, 3400 Civic Center Boulevard, Building 421, Philadelphia, Pennsylvania 19104.
• Quantitative multiplexed immune-phenotyping of cardiac allograft biopsies provides novel diagnostic and prognostic information about allograft health.
• Reduced proportions of cells expressing PD-L1 and FoxP3 are associated with clinical evidence of serious allograft injury, even when conventional histologic analysis provides falsely reassuring histologic rejection grades.
• The proportions of PD-L1- and FoxP3-expressing cells are dynamic within cardiac allografts, and reduced levels can precede future rejection.
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.
Research reported in this publication was supported by the Gund Family Fund at the University of Pennsylvania and the National Center for Advancing Translational Sciences of the National Institutes of Health under award number TL1TR001880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mr. Wang, Ms. Ishola, and Ms. Remeniuk are employed by Akoya Biosciences. Mr. Hoyt is employed by Akoya Biosciences; and owns Akoya Biosciences stock and stock options. Dr. Feldman is an equity holder and has technology licensed to both Elucid Bioimaging and Inspirata Inc.; has served as a scientific advisory consultant for Inspirata Inc.; served on the scientific Advisory Board of Inspirata Inc.; and has consulted for Phillips Healthcare, XFIN, and Virbio. Dr. Margulies has received research grants from Thoratec Corporation, Merck, Sanofi-Aventis USA, and GlaxoSmithKline; has served as a scientific consultant for American Regent; and has served as an Advisory Board member for Pfizer and MyoKardia. Dr. Peyster has reported that he has no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received December 15, 2019.
- Revision received January 24, 2020.
- Accepted January 24, 2020.
- 2020 The Authors