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Updated: Jul 29, 2026
High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease
Published on: October 31, 2012
Whole Transcriptome Sequencing Identified Potential Serum Protein Markers for the Diagnosis of Antibody Mediated
Yuanyi Mang1, Yinjia Wang2, Wang Li1
1Department of Hepatobiliary and Liver Transplantation Surgery, The First People's Hospital of Yunnan Province. The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, People's Republic of China.
Background:
Antibody medicated rejection is a challenging condition for patients undergoing liver transplantation. This study aims to investigate the mechanism of AMR and identify potential serum ma`rkers for AMR diagnosis.
Method:
The liver tissue of 4 patients with AMR and 4 patients without AMR were collected. Whole transcriptome sequencing (RNA-seq) was performed to compare the transcriptomic alterations between the 2 groups of patients, and between tissues obtained before AMR and after AMR cure. Mass spectrometry was also performed to compare the serum proteomic changes of the 2 groups.
Results:
Transcriptomic analysis between patients with and without AMR revealed differential expression of mRNA, lncRNA and circRNA. Analysis of differential mRNA revealed the alterations of CD and IL markers, possibly involving M1 macrophages, T cells and dendritic cells. The fold changes of mRNA levels of HLA type I and II molecules between 1.57 and 3.13 (P < .05) suggested increased expression of HLA in all nucleated cells. In contrast, significant alterations in lncRNA and circRNA linked genes suggested comprehensive up- or down-regulations in T, B, NK cells, DCs and monocytes. Serum protein analysis between patients with or without AMR identified significant down-regulation of complement C3 (fold change: 0.63, P = .028), C6 (fold change: 0.72, P = .05), C8 (fold change: 0.67, P = .020), factor H (fold change: 0.54, P = .007), and C4-binding proteins(fold change: 0.70, P = .025), and significant up-regulation of HLA class I molecules(fold change: 2.53, P = .006), IgKappa (fold change: 2.17, P = .023), low-affinity IgGamma (fold change: 1,74, P = .024), which could be potential serum markers for AMR. Further transcriptomic analysis revealed comprehensive and unspecific alterations of immune cell levels, HLA antigen levels and cytokine expression in patients recovered from AMR following treatment, suggesting the presence of immune changes even after AMR cure.
Conclusions:
AMR caused a wide range of changes in the cellular microenvironment in the graft liver, including cell composition, antigen expression and cytokine expression. A panel of serum protein markers related to AMR has been identified and may potentially be used for ARM diagnosis.
