Case Control Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2025; 17(8): 109685
Published online Aug 27, 2025. doi: 10.4254/wjh.v17.i8.109685
Peripheral basophil activation: A hidden player in the immunopathogenesis of primary biliary cholangitis
Huan-Qin Han, Jia-Min Bao, Wei Deng, Wei-Fang Guo, Yi-Fan Li, Wei-Qiang Zheng, Hua-Feng Liu
Huan-Qin Han, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
Huan-Qin Han, Jia-Min Bao, Wei Deng, Wei-Fang Guo, Yi-Fan Li, Wei-Qiang Zheng, Department of Infectious Diseases and Hepatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, China
Hua-Feng Liu, Department of Nephrology, National Clinical Key Specialty Construction Program (2023), Institute of Nephrology, Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, China
Co-first authors: Huan-Qin Han and Jia-Min Bao.
Author contributions: Han HQ obtained funding and designed the study; Han HQ, Bao JM, Deng W, Guo WF, and Li YF collected clinical data and followed up the patients; Han HQ and Bao JM were responsible for the cell experiment detection and manuscript writing; Liu HF and Zheng WQ guided this research and revised the manuscript. All authors contributed to the interpretation of the study and approved the final version to be published.
Supported by Guangdong Provincial Basic and Applied Basic Research Fund, No. 2021A1515011589; and Guangdong Medical University Clinical + Basic Science and Technology Innovation Special Program, No. GDMULCJC2024004.
Institutional review board statement: This study was approved by the Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Approval No.: YS2020-115).
Informed consent statement: Informed consent was obtained from the participants in accordance with the guidelines of the Declaration of Helsinki.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: No additional data are available.
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: Hua-Feng Liu, MD, PhD, Chief Physician, Professor, Department of Nephrology, National Clinical Key Specialty Construction Program (2023), Institute of Nephrology, Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, No. 57 South Renmin Road, Zhanjiang 524001, Guangdong Province, China. liuhf@gdmu.edu.cn
Received: May 19, 2025
Revised: June 18, 2025
Accepted: July 18, 2025
Published online: August 27, 2025
Processing time: 101 Days and 1.1 Hours
Abstract
BACKGROUND

T helper 17 (Th17) cell infiltration and interleukin (IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis (PBC). IL-6 is an essential upstream activator of Th17 cells. Basophil-derived IL-6 promotes the differentiation of CD4+ T cells and Th1 cells into Th17 cells, thereby regulating their immunological functions.

AIM

To investigate the activation status and cytokine expression of basophils in PBC, elucidating potential mechanisms through which basophils contribute to its pathogenesis.

METHODS

This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital (China) between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC (PBC group), 65 age- and sex-matched patients with chronic hepatitis B (CHB group), and 65 healthy controls (Normal group). Fourteen participants per group (subgroup) were randomly selected for flow cytometry analysis of basophil proportion, activation markers (CD203c and CD62 L mean fluorescence intensity), IL-6-positive basophils (IL-6+ basophils as a percentage of total basophils), and IL-17-positive T lymphocytes (CD3+CD4+IL-17+ cells) proportion among T cells. Data were analyzed using Kruskal-Wallis and χ2 tests as appropriate.

RESULTS

Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups (P < 0.001 for both comparisons), with no significant differences between the CHB and Normal groups (P = 0.201). Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB (P = 0.011) and Normal subgroups (P < 0.001). The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB (P = 0.032) and Normal subgroups (P = 0.039). The proportion of IL-6+ basophils was significantly higher in the PBC subgroup than in the CHB (P < 0.01) and Normal subgroups (P < 0.001). Similarly, the Th17 cell proportion was markedly elevated in the PBC compared to the CHB (P < 0.001) and Normal subgroups (P < 0.001).

CONCLUSION

Patients with PBC have increased peripheral basophil counts with enhanced activation. Activated basophils have increased IL-6 expression, which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.

Keywords: Primary biliary cholangitis; Basophils; Immunopathogenesis; T helper 17 Cells; CD4+T lymphocytes

Core Tip: Peripheral basophil counts and proportions were significantly elevated in patients with primary biliary cholangitis (PBC), with increased expression of the activation marker CD203c mean fluorescence intensity and intracellular interleukin (IL)-6. Concurrently, CD4+ T lymphocytes in patients with PBC showed markedly increased IL-17 expression. These findings suggest that activated basophils, through IL-6 upregulation, may promote T helper 17 cell proliferation and promote PBC pathogenesis.