Serum CA125 for Detection of Antibody-Mediated Rejection in Heart Transplantation Recipients

Although the potential role of carbohydrate antigen 125 (CA125) in acute cellular rejection (ACR) has been explored, its role in antibody-mediated rejection (AMR) remains unclear. Since CA125 is associated with inflammation and congestion, we hypothesized that CA125 could reflect key processes in AMR and complement the existing diagnostic methods. We analyzed 491 serum samples from heart transplant recipients undergoing first-year routine endomyocardial biopsies (EMBs). The results of EMB were classified as no-rejection, ACR, or AMR. CA125 levels were measured using a chemiluminescent immunoassay. CA125 concentrations were significantly higher in the AMR group (median 41 [IQR 26–78] U/mL) than in the no-rejection group (median 17 [IQR 11–27] U/mL; p < 0.01), regardless of post-transplantation time. In contrast, no significant differences were observed between the ACR and no-rejection groups (p = 0.124). Receiver operating characteristic analysis demonstrated strong diagnostic performance of CA125 for AMR (area under the curve = 0.821; p < 0.001). CA125 was an independent predictor of AMR (odds ratio, 5.04; p < 0.01). Our results demonstrated that elevated circulating CA125 levels are associated with AMR and exhibit promising diagnostic performance after heart transplantation, highlighting their potential as a non-invasive biomarker. This is further supported by the wide availability, standardization, and reproducibility of CA125 measurements in clinical practice.