Identifying low-grade cellular rejection after heart transplantation in children using gene expression profiling

Xin, A; Lee, MGY; Hu, Y; Ignjatovic, V; Shi, WY; Shipp, A; Praporski, S; Kallies, A; Weintraub, RG; Monagle, PT; Smyth, GK; Konstantinov, I

Author(s): Xin, A; Lee, MGY; Hu, Y; Ignjatovic, V; Shi, WY; Shipp, A; Praporski, S; Kallies, A; Weintraub, RG; Monagle, PT; Smyth, GK; Konstantinov, I;
Details: Publication Year 2018,Volume 50,Issue #3,Page 190-196
Journal Title: Physiological Genomics
Publication Type: Journal Article
Abstract: BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection after heart transplantation but is costly and invasive. This study aims to distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart transplantation in children by global gene expression profiling in blood. METHODS: A total of 106 blood samples with corresponding EMB from 18 children who underwent heart transplantation from 2011-2014 were analyzed (18 baseline/pre-transplantation samples, 88 EMB samples). Corresponding rejection grades for each blood sample was 0R in 39% (34/88), 1R in 51% (45/88), and 2R in 10% (9/88). mRNA from each sample was sequenced. Differential expression analysis was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied to the most differentially expressed (DE) genes to identify rejection after transplantation. RESULTS: Mean age at transplantation was 10.0 {plus minus} 5.4 years. Expression of B cell and T cell receptor sequences were used to measure the effect of post-transplantation immunosuppression. Follow-up samples had lower levels of immunoglobulin gene families compared to pre-transplantation (p<3E-5) (lower numbers of activated B cells). T cell receptor alpha and beta gene families had decreased expression in 0R samples compared to pre-transplantation (p<4E-5), but recovered to near baseline levels in 1R/2R samples. kNN using the most DE gene (MKS1) and k=9 nearest neighbors correctly identified 83% (73/88) of 1R/2R compared to 0R by leave-one-out cross validation. CONCLUSIONS: Low-grade cellular allograft rejection (1R/2R) can be distinguished from no rejection (0R) after heart transplantation in children using a genomic approach despite a wide age range.
Keywords: Gene expression profiling; Heart transplantation; Msk1; Rejection
Research Division(s): Molecular Immunology; Bioinformatics
PubMed ID: 29341866
Publisher's Version: https://doi.org/10.1152/physiolgenomics.00046.2017
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2018-01-23 10:22:55

Last Modified: 2018-07-09 03:32:24