Document Type
Article
Publication Date
2-1-2026
Abstract
Background: Acute cellularrejection (ACR) remains a major cause of morbidity afterhearttransplantation despite advances in immunosuppression. Whole genometranscriptomicprofiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive,longitudinal biomarker assessments capable of capturing the temporal dynamics ofrejection biology remain scarce.
Methods: RNA sequencing ofperipheralblood fromheart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assessgene-based prediction of ACR.
Results: A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning-based classifier, DYNLL1 and SERF2 were identified as ACR predictive genes, and achieved a cross-validated area under the receiver operating characteristic curve of 0.63.
Conclusions: Peripheralbloodtranscriptomics identify dynamic temporal responses in ACR including T- and B-cell pathways with potential ACR predictive genes that warrant further investigation.
Recommended Citation
Ghazal, Rachad; Wang, Min; Srinivas, Akshatha N.; Cao, Jenny J.; Vyas, Hridyanshu; Liu, Duan; Nair, Asha; Smith, Byron H.; Wang, Li; Yip, Daniel S.; Patel, Parag C.; Steidley, David E.; Hardaway, Brian W.; Clavell, Alfredo L.; Kushwaha, Sudhir S.; Park, Walter D.; Stegall, Mark D.; Eisen, Howard; and Pereira, Naveen L., "Longitudinal Peripheral Blood Transcriptomics Reveal Novel Signatures During Cardiac Allograft Rejection." (2026). Division of Cardiology Faculty Papers. Paper 193.
https://jdc.jefferson.edu/cardiologyfp/193
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
PubMed ID
41567756
Comments
This article is the author's final published version in Transplantation Direct, Volume 12, Issue 2, February 2026, Article Number e1882.
The published version is available at https://doi.org/10.1097/TXD.0000000000001882. Copyright © 2026 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.