STXBP3 and GOT2 predict immunological activity in acute allograft rejection

Abstract

BackgroundAcute allograft rejection (AR) following renal transplantation contributes to chronic rejection and allograft dysfunction. The current diagnosis of AR remains dependent on renal allograft biopsy which cannot immediately detect renal allograft injury in the presence of AR. In this study, sensitive biomarkers for AR diagnosis were investigated and developed to protect renal function.MethodsWe analyzed pre- and postoperative data from five databases combined with our own data to identify the key differently expressed genes (DEGs). Furthermore, we performed a bioinformatics analysis to determine the immune characteristics of DEGs. The expression of key DEGs was further confirmed using the real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemical (IHC) staining in patients with AR. ROC curves analysis was used to estimate the performance of key DEGs in the early diagnosis of AR.ResultsWe identified glutamic-oxaloacetic transaminase 2 (GOT2) and syntaxin binding protein 3 (STXBP3) as key DEGs. The higher expression of STXBP3 and GOT2 in patients with AR was confirmed using RT-qPCR, ELISA, and IHC staining. ROC curve analysis also showed favorable values of STXBP3 and GOT2 for the diagnosis of early stage AR.ConclusionsSTXBP3 and GOT2 could reflect the immunological status of patients with AR and have strong potential for the diagnosis of early-stage AR.

Sex differences in brain protein expression and disease

“…In AD, both human and mouse studies using brain transcriptomic data also observed the prominent role of microglial and inflammatory mechanisms in sex differences in AD 31 , 32 . In agreement with these results, among the eight AD causal genes with either sex-biased expression or genetic regulation of protein expression that we identified, half of them are involved in immune function: CD2AP facilitates recognition of antigen by T cells 42 ; SLMAP participates in T cell receptor signaling 43 ; ADAM10 regulates cytokine levels in activated microglia 44 ; and STXBP3 is involved in immune function 45 , 46 .…”

Profiling Cancer-Associated Fibroblasts (CAFs) in Gastric Cancer and Development of a CAF-Based Prognostic Signature Using Integrated Single-Cell RNA Sequencing and TCGA Analysis

“…Further correlational analyses between these five genes and 39 pathways unveiled distinct pathway signatures for protective and risk genes. Protective genes exhibited positive associations with pathways such as allograft rejection, myogenesis, complement, and interferon-gamma response, whereas risk genes were tied to fatty acid metabolism, xenobiotic metabolism, and adipogenesis [32,33]. Alterations in fatty acid metabolism have been implicated in GC pathogenesis, with demonstrated prognostic value of fatty acid metabolism-related genes [34][35][36].…”

Increasing Eligibility to Transplant Through the Selective Cytopheretic Device: A Review of Case Reports Across Multiple Clinical Conditions

“… 33 Circulating innate immune cells such as monocytes and dendritic cells have also been implicated in acute rejection, a key concern for kidney rejection, with genes such as aspartate aminotransferase demonstrating enriched expression in these cells. 34 Yet another process affecting kidney allograft and function is brain death associated inflammation; however, the pathophysiological process has been unclear. A recent report by Zitur et al 35 demonstrated an upregulation in circulating leukocytes and cytokines, activation of complement and coagulation pathways, and upregulation of genes associated with inflammation in both brain-dead and sham subjects relative to naive controls in a rhesus macaque disease model.…”