Anti-RPL30 as a novel biomarker for enhanced diagnosis of autoantibody-negative primary biliary cholangitis

The diagnosis of primary biliary cholangitis (PBC) remains challenging, particularly in cases where anti-mitochondrial antibody (AMA), anti-mitochondrial E2 subunit antibody (AMA-M2), anti-glycoprotein 210 (anti-gp210), and anti-speckled protein 100 (anti-Sp100) are all negative. In such instances, the condition is often confirmed through a liver needle biopsy.

To identify additional plasma biomarkers for non-invasive diagnostic methods of PBC.

We utilized the Sengenics KREX™ immunome protein array to identify potential biomarkers for the diagnosis of PBC. Subsequently, we validated the predictive capability of the RPL30 antibody through an ELISA and retrospectively analyzed its association with the clinical features of 17 autoantibody-negative PBC cases and 45 autoantibody-positive PBC cases.

In our study we observed that RPL30 demonstrated the highest fold-change difference in PBC, with a penetrance frequency of 40% and a penetrance fold change of 38.30147. The analysis of anti-RPL30 optical density values between patients with AMA/AMA-M2/anti-gp210/anti-Sp100-negative PBC (autoantibody-negative PBC) and healthy controls using a receiver operating characteristic curve yielded an area under the curve of 0.853. This analysis established an optimal cutoff value of 0.0708, achieving 100% specificity and 75% sensitivity. The combination of anti-RPL30 and other autoantibodies elevated the diagnosis rate of PBC from 61.29% to 79.00% (P = 0.0489). Anti-RPL30 demonstrated a high positive rate in antibody-negative PBC cases, including AMA/AMA-M2/anti-gp210/anti-Sp100-negative cases. Correlation analysis of anti-RPL30 optical density values with clinical data from patients with PBC revealed a positive association with both the international normalized ratio (P = 0.008) and the Model for End-Stage Liver Disease score (P = 0.003).

Our study highlighted the potential of anti-RPL30 as a promising biomarker for diagnosing PBC, particularly in autoantibody-negative cases.