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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Decreased of BAFF-R expression and B cells maturation in patients with hepatitis B virus-related hepatocellular carcinoma
Apichaya Khlaiphuengsin, Natthaya Chuaypen, Pimpayao Sodsai, Supranee Buranapraditkun, Tadech Boonpiyathad, Nattiya Hirankarn, Pisit Tangkijvanich
Apichaya Khlaiphuengsin, Natthaya Chuaypen, Pisit Tangkijvanich, Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Pimpayao Sodsai, Nattiya Hirankarn, Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Supranee Buranapraditkun, Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Supranee Buranapraditkun, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
Supranee Buranapraditkun, Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Tadech Boonpiyathad, Department of Medicine, Phramongkutklao Hospital, Bangkok 10400, Thailand
Author contributions: Khlaiphuengsin A designed the research, performed the research and drafted the manuscript; Chuaypen N, Sodsai P and Buranapraditkun S supervised the report and contributed to the analysis; Boonpiyathad T and Hirankarn N supervised the report; Tangkijvanich P provided clinical advice, drafted and approved the final version of the manuscript.
Supported by the Thailand Research Fund, No. RTA6280004; the Grant for Chula Research Scholar, No. CU-GRS-61-07-30-02; Second Century Fund (C2F), Chulalongkorn University; and the Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University.
Institutional review board statement: The study was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (IRB no. 438/60).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Pisit Tangkijvanich, MD, Doctor, Professor, Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand. pisittkvn@yahoo.com
Received: January 27, 2020
Peer-review started: February 03, 2020
First decision: February 29, 2020
Revised: March 27, 2020
Accepted: May 13, 2020
Article in press: May 13, 2020
Published online: May 28, 2020
BACKGROUND
Recent evidence has indicated the role of B cells and B cell-activating factor (BAFF) in the development of hepatocellular carcinoma (HCC).
AIM
To characterize circulating BAFF receptor expression and B cell subpopulations in patients with hepatitis B virus (HBV)-related HCC.
METHODS
Peripheral blood samples collected from 41 patients with chronic HBV infection (25 patients without HCC and 16 patients with HCC) and 9 healthy controls were assessed for BAFF receptors [BAFF-R(B cell-activating factor receptor), transmembrane activator and cyclophilin ligand interactor, B-cell maturation antigen] and B cell subpopulations by multicolor flow cytometry.
RESULTS
The frequency of BAFF-R expressing B cells to total B cells was significantly lower in patients with HCC (3.39% ± 2.12%) compared with the non-HCC group (5.37% ± 1.90%) and healthy controls (6.23% ± 2.32%), whereas there was no difference in transmembrane activator and cyclophilin ligand interactor and B-cell maturation antigen. The frequencies of CD27+IgD+ memory B cells, CD27+IgD- class-switched memory B cells and plasmablasts were significantly lower in the patients with HCC compared to patients without HCC (1.23 ± 1.17 vs 3.09 ± 1.55, P = 0.001, 0.60 ± 0.44 vs 1.69 ± 0.86, P < 0.0001 and 0.16 ± 0.12 vs 0.37 ± 0.30, P = 0.014, respectively). However, the ratio of naïve and transitional B cell did not differ significantly between the three groups. In addition, decreased BAFF-R expression on B cells was significantly correlated with large tumor size and advanced tumor stage.
CONCLUSION
Our data demonstrated BAFF-R expression was reduced in B cells that involved with the frequencies of B cells maturation in patients with HCC. The depletion of BAFF-R might play an important role in the development of HCC in patients with chronic HBV infection.
Core tip: This study explored the expression of B cell-activating factor receptor (BAFF-R) and B cell subpopulations in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Our data showed that BAFF-R expression was significantly lower in patient with HCC compared with non-HCC and healthy controls. In addition, the frequencies of CD27+IgD+ memory B cells, CD27+IgD- class-switched memory B cells and plasmablasts were significantly lower in the patients with HCC compared to patients without HCC. In addition, decreased BAFF-R expression was significantly correlated with tumor size and tumor stage. This study is the first report suggesting that the depletion of BAFF-R in B cells might be responsible for B cell maturation in patients with HBV-related HCC.
