Objective:

To analyze gene expression differential patterns for acute rejection versus non-rejection and identify enriched Reactome pathways associated with acute rejection, highlighting their clinical significance.

Key Findings:

• A total of 1,032 genes were differentially expressed (FDR1.
• Upregulated genes included HLA-DMA, DEF6, TRB@, and CD74.
• Enrichment analysis highlighted interferon signaling, T-cell receptor signaling, chemokine pathways, and antigen presentation.
• Immune scoring indicated increased monocytic, B-lineage, and T/cytotoxic lymphocyte signals in rejection.
• The diagnostic model achieved strong discrimination (5-fold AUC=0.993).

Interpretation:

Acute rejection EMB transcriptomes demonstrate coordinated interferon-driven immune activation, with a compact gene signature showing strong internal diagnostic performance.

Limitations:

• The study relies on a single dataset, which may limit generalizability and introduce biases.
• Variability in reported signatures exists between cohorts and research platforms, which may affect the robustness of findings.

Conclusion:

The findings warrant external confirmation for the identified gene signature and its potential utility in clinical decision support, emphasizing the need for further validation in diverse populations.