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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Anti-RPL30 as a novel biomarker for enhanced diagnosis of autoantibody-negative primary biliary cholangitis
Zhi-Yu Zeng, Zu-Xiong Huang, Yi-Ran Wang, Long-Ke Xie, Yi-Ping Lin, Ying Liang, Zi-Ying Liu, Dong-Liang Li, Xiao-Yong Zhang
Zhi-Yu Zeng, Yi-Ran Wang, Zi-Ying Liu, Xiao-Yong Zhang, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Zhi-Yu Zeng, Ying Liang, Dong-Liang Li, Department of Hepatobiliary Disease, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou 350025, Fujian Province, China
Zhi-Yu Zeng, Yi-Ran Wang, Zi-Ying Liu, Xiao-Yong Zhang, Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Guangdong Institute of Hepatology, Guangzhou 510515, Guangdong Province, China
Zu-Xiong Huang, Department of Liver Diseases, MengChao Hepatobiliary Hospital, Fujian Medical University, Fuzhou 350025, Fujian Province, China
Long-Ke Xie, Department of Gastroenterology, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou 350025, Fujian Province, China
Yi-Ping Lin, Department of Health and Medicine, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou 350025, Fujian Province, China
Co-first authors: Zhi-Yu Zeng and Zu-Xiong Huang.
Co-corresponding authors: Dong-Liang Li and Xiao-Yong Zhang.
Author contributions: Zeng ZY, Huang ZX, Li DL, and Zhang XY were responsible for conceptualization, supervision, reviewing, and editing; Zeng ZY, Wang YR, Xie LK, Liu ZY, and Lin YP were responsible for data curation, formal analysis, investigation, resources, and software; Zeng ZY and Ying L were responsible for methodology, project administration, and writing the original draft; Zeng ZY and Zhang XY were responsible for funding acquisition.
Supported by National Natural Science Foundation of China, No. 82172257; Health Care Major Project of Guangzhou, No. 202206080001; and Science and Technology Cooperation Program of Fujian Province, No. 2021I0036.
Institutional review board statement: This study was approved by the Ethics Committee of 900th Hospital of PLA (No. 2022-054). Written informed consent was obtained from all participants.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data sharing statement: The dataset is available from the corresponding author upon request at
xiaoyzhang@smu.edu.cn.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Xiao-Yong Zhang, MD, PhD, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong Province, China.
xiaoyzhang@smu.edu.cn
Received: January 7, 2025
Revised: March 29, 2025
Accepted: May 6, 2025
Published online: May 28, 2025
Processing time: 141 Days and 23.4 Hours
BACKGROUND
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.
AIM
To identify additional plasma biomarkers for non-invasive diagnostic methods of PBC.
METHODS
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.
RESULTS
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).
CONCLUSION
Our study highlighted the potential of anti-RPL30 as a promising biomarker for diagnosing PBC, particularly in autoantibody-negative cases.
Core Tip: The diagnosis of autoantibody-negative primary biliary cholangitis (PBC) remains challenging and is typically confirmed through liver needle biopsy. Using the immunome protein array, RPL30 was identified as a novel biomarker for PBC. Validation of the RPL30 autoantibody through ELISA analysis showed a higher positivity rate in autoantibody-negative PBC cases, including anti-mitochondrial antibody, anti-mitochondrial E2 subunit antibody, anti-glycoprotein 210, and anti-speckled protein 100-negative cases compared with the healthy control group. Anti-RPL30 improved the diagnostic rate of antibody-negative PBC and correlated with hepatic damage, poorer synthetic function, and higher Model for End-Stage Liver Disease scores.
