Fibrosis Process Activation in Patients with Acute Cardiac Rejection: A Novel Noninvasive Diagnostic Approach

Background/Objectives: Cardiac allograft fibrosis is an important limiting factor for long-term graft survival. However, the fibrotic process operating in patients with acute cellular rejection (ACR) remains unclear. We aimed to identify altered serum mRNAs related to cardiac fibrosis in patients with ACR and to evaluate their diagnostic accuracy in detecting rejection episodes. Methods: We included 40 serum samples from recipients of transplants undergoing routine endomyocardial biopsies. Results: Several altered mRNAs associated with fibrosis were detected in patients with ACR. Specifically, the activators of fibroblasts and myofibroblasts (TNS1, FAP and ACTA2), TGF-β signaling (TGFBR1 and JAK1) and WNT signaling (WNT7A and WLS) pathways were significantly different when we compared grade ≥ 2R ACR and/or grade 1R ACR groups with the nonrejection group. Furthermore, TNS1 and WLS presented an area under the curve value > 0.90 for identifying patients with moderate and severe grades of cardiac rejection. Conclusions: In conclusion, we found alterations in the relative abundance of circulating activators of fibroblasts and myofibroblasts, such as FAP or ACTA2, as well as in major profibrotic pathways, including TGF-β and WNT signaling, especially in clinically relevant cardiac rejection. These findings may contribute to improving the surveillance of patients with cardiac transplant and provide new therapeutic strategies for targeting fibrosis process activation.