TY - JOUR
T1 - In Situ Immune Profiling of Heart Transplant Biopsies Improves Diagnostic Accuracy and Rejection Risk Stratification
AU - Peyster, Eliot G.
AU - Wang, Chichung
AU - Ishola, Felicia
AU - Remeniuk, Bethany
AU - Hoyt, Clifford
AU - Feldman, Michael D.
AU - Margulies, Kenneth B.
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2020 The Authors
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - allograft rejection
KW - immune checkpoint molecules
KW - immune regulation
KW - quantitative immunohistochemistry
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UR - http://www.scopus.com/inward/citedby.url?scp=85083377005&partnerID=8YFLogxK
U2 - 10.1016/j.jacbts.2020.01.015
DO - 10.1016/j.jacbts.2020.01.015
M3 - Article
C2 - 32368693
AN - SCOPUS:85083377005
SN - 2452-302X
VL - 5
SP - 328
EP - 340
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 4
ER -