AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025230234
ORIGINAL RESEARCH ARTICLE

Characteristics of T-cell and B-cell receptor repertoires in patients with autoimmune hepatitis

Junning Zhang1† Zhihui Feng1† Biao Zhang1 Yi Liu1 Chunhong Li1 Meng Meng1 Fei Yang1 Man Yang1 Xianliang Hou1,2*
Show Less
1 Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Department of Central Laboratory, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
2 Department of Central Laboratory, Shenzhen Hospital (Longgang), Beijing University of Chinese Medicine, Shenzhen, Guangdong, China
†These authors contributed equally to this work.
Received: 2 June 2025 | Revised: 27 August 2025 | Accepted: 25 September 2025 | Published online: 27 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease characterized by inflammation resulting from the body’s immune system attacking its own liver cells. T-cell receptor (TCR) and B-cell receptor (BCR) repertoires are crucial mediators of autoimmune diseases, with the cause of B-lineage dysregulation remaining elusive.

Objective: This study aims to comprehensively describe the changes in TCR and BCR repertoires in the peripheral blood and liver of patients with AIH.

Methods: High-throughput sequencing and multiplex polymerase chain reaction amplification were applied to explore the TCR and BCR gene repertoire characteristics in 60 patients with AIH and control groups.

Results: The findings revealed a significant reduction in the diversity of BCR heavy-chain (BCR-H) repertoire and the length of BCR-H complementarity-determining region 3 (CDR3) in the peripheral blood of AIH patients. Interestingly, the pre-selection BCR-H CDR3s in AIH patients were abnormally short, suggesting irregularities in the early stages of B-cell development and repertoire formation in the bone marrow. Furthermore, compared with controls, peripheral blood samples from AIH patients showed reduced diversity in the TCR β-chain (TCR-β) repertoire, longer CDR3 lengths, biased TCR-β variable gene usage, and extensive TCR-β sharing. The analysis revealed a comparable distribution of clone diversity between liver tissue samples from AIH and control groups, potentially attributable to the architectural characteristics of AIH liver T and B cells, which are marked by the presence of multiple antigen-responsive T and B cells rather than a single reactive T and B lymphocyte clone.

Conclusion: This study reveals distinct alterations in the TCR and BCR repertoires among patients with AIH, potentially offering novel insights for its prevention and diagnosis.

Keywords
T cell receptor
Immunoglobulin heavy chain
Immune repertoire
High-throughput sequencing
Autoimmune hepatitis
Funding
This work was supported by the Guangdong Basic and Applied Basic Research Foundation (2025A1515012661); Guangxi Natural Science Foundation (2024GXNSFAA010096); Shenzhen Science and Technology Program (JCYJ20230807150913027 and JCYJ20240813165111016); Guilin Science Research and Technology Development Project (20230135- 4-2 20220139-13-2); Guangdong Province Medical Science and Technology Research Fundation (B2025207); Guangxi Medical and Health Appropriate Technology Development and Promotion Project (S2024075); the National Natural Science Foundation of China (82460324 and 82101877); China Postdoctoral Science Foundation (2023M740344); Innovation Training Program for College Students (202410601013 and S202410601182); Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation (2023KF006, 3030302213, and 2021KF001); and Guangxi Medical and Health Key Cultivation Discipline Construction Project.
Conflict of interest
The authors declare no competing interests.
References
  1. Cheng Z, Yang L, Chu H. The gut microbiota: A novel player in autoimmune hepatitis. Front Cell Infect Microbiol. 2022;12:947382. doi: 10.3389/fcimb.2022.947382

 

  1. Sirbe C, Simu G, Szabo I, Grama A, Pop TL. Pathogenesis of autoimmune hepatitis-cellular and molecular mechanisms. Int J Mol Sci. 2021;22(24):13578. doi: 10.3390/ijms222413578

 

  1. Boer YS, Van Gerven NM, Zwiers A, et al. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1. Gastroenterology. 2014;147(2):443-452.e5. doi: 10.1053/j.gastro.2014.04.022

 

  1. Browning JL. B cells move to centre stage: Novel opportunities for autoimmune disease treatment. Nat Rev Drug Discov. 2006;5(7):564-576. doi: 10.1038/nrd2085

 

  1. Schultheiß C, Simnica D, Willscher E, et al. Next-generation immunosequencing reveals pathological T-cell architecture in autoimmune hepatitis. Hepatology. 2021;73(4);1436-1448. doi: 10.1002/hep.31473

 

  1. Dziubianau M, Hecht J, Kuchenbecker L, et al. TCR repertoire analysis by next generation sequencing allows complex differential diagnosis of T cell-related pathology. Am J Transplant. 2013;13(11):2842-2854. doi: 10.1111/ajt.12431

 

  1. Monod MY, Giudicelli V, Chaume D, Lefranc MP. IMGT/JunctionAnalysis: The first tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J JUNCTIONs. Bioinformatics. 2004;20(Suppl 1);i379-i385. doi: 10.1093/bioinformatics/bth945

 

  1. Robins H, Desmarais C, Matthis J, et al. Ultra-sensitive detection of rare T cell clones. J Immunol Methods. 2012;375(1-2):14-19. doi: 10.1016/j.jim.2011.09.001

 

  1. Kitaura K, Yamashita H, Ayabe H, Shini T, Matsutani T, Suzuki R. Different somatic hypermutation levels among antibody subclasses disclosed by a new next-generation sequencing-based antibody repertoire analysis. Front Immunol. 2017;8:389. doi: 10.3389/fimmu.2017.00389

 

  1. Carlson CS, Emerson RO, Sherwood AM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4(1):2680. doi: 10.1038/ncomms3680

 

  1. Bolotin DA, Poslavsky S, Mitrophanov I, et al. MiXCR: Software for comprehensive adaptive immunity profiling. Nat Methods. 2015;12(5):380-381. doi: 10.1038/nmeth.3364

 

  1. Stewart JJ, Lee CY, Ibrahim S, et al. A shannon entropy analysis of immunoglobulin and T cell receptor. Mol Immunol. 1997;34(15):1067-1082. doi: 10.1016/S0161-5890(97)00130-2

 

  1. Venturi V, Kedzierska K, Turner SJ, Doherty PC, Davenport MP. Methods for comparing the diversity of samples of the T cell receptor repertoire. J Immunol Methods. 2007;321(1-2):182-195. doi: 10.1016/j.jim.2007.01.019

 

  1. Gomez-Tourino I, Kamra Y, Baptista R, Lorenc A, Peakman M. T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes. Nat Commun. 2017;8(1):1792. doi: 10.1038/s41467-017-01925-2

 

  1. Hou X, Wang G, Fan W, et al. T-cell receptor repertoires as potential diagnostic markers for patients with COVID-19. Int J Infect Dis. 2021;113:308-317. doi: 10.1016/j.ijid.2021.10.033

 

  1. Wu J, Liu D, Tu W, Song W, Zhao X. T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2015;135(1):209-216. doi: 10.1016/j.jaci.2014.06.025

 

  1. Miqueu P, Guillet M, Degauque N, Doré JC, Soulillou JP, Brouard S. Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases. Mol Immunol. 2007;44(6):1057-1064. doi: 10.1016/j.molimm.2006.06.026

 

  1. Lee YN, Frugoni F, Dobbs K, et al. Characterization of T and B cell repertoire diversity in patients with RAG deficiency. Sci Immunol. 2016;1(6):eaah6109. doi: 10.1126/sciimmunol.aah6109

 

  1. Stadinski BD, Shekhar K, Gómez-Touriño I, et al. Hydrophobic CDR3 residues promote the development of self-reactive T cells. Nat Immunol. 2016;17(8):946-955. doi: 10.1038/ni.3491

 

  1. Mieli-Vergani G, Vergani D, Czaja AJ, et al. Autoimmune hepatitis. Nat Rev Dis Primers. 2018;4(1):18017. doi: 10.1038/nrdp.2018.17

 

  1. Liberal R, Longhi MS, Mieli-Vergani G, Vergani D. Pathogenesis of autoimmune hepatitis. Best Pract Res Clin Gastroenterol. 2011;25(6):653-664. doi: 10.1016/j.bpg.2011.09.009

 

  1. Bao J, Xu Q, Zou Y, et al. Deep sequencing of the T cell receptor Vb CDR3 repertoire of peripheral CD4+T cells in primary biliary cirrhosis. Zhonghua Gan Zang Bing Za Zhi. 2015;23(8):580-585. doi: 10.3760/cma.j.issn.1007-3418.2015.08.005

 

  1. Miyama T, Kawase T, Kitaura K, et al. Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals. Sci Rep. 2017;7(1):3663. doi: 10.1038/s41598-017-03855-x

 

  1. Hou X, Wei W, Zhang J, et al. Characterisation of T and B cell receptor repertoire in patients with systemic lupus erythematosus. Clin Exp Rheumatol. 2023;41(11):2216-2223. doi: 10.55563/clinexprheumatol/1rjr4s

 

  1. Hou X, Chen W, Zhang X, et al. Preselection TCR repertoire predicts CD4+ and CD8+ T‐cell differentiation State. Immunology. 2020;161(4):354-363. doi: 10.1111/imm.13256

 

  1. Li Y, Geng S, Du X, et al. Restricted TRBV repertoire in CD4+ and CD8+ T‐cell subsets from CML patients. Hematology. 2011;16(1):43-49. doi: 10.1179/102453311X12902908411634

 

  1. Lu C, Pi X, Xu W, et al. Clinical significance of T cell receptor repertoire in primary Sjogren’s syndrome. EBioMedicine. 2022;84:104252. doi: 10.1016/j.ebiom.2022.104252

 

  1. Hou X, Yang Y, Chen J, et al. TCRβ repertoire of memory T cell reveals potential role for Escherichia coli in the pathogenesis of primary biliary cholangitis. Liver Int. 2019;39(5):956-966. doi: 10.1111/liv.14066

 

  1. Zhang L, Jiao W, Deng H, et al. High-throughput treg cell receptor sequencing reveals differential immune repertoires in rheumatoid arthritis with kidney deficiency. PeerJ. 2023;11:e14837. doi: 10.7717/peerj.14837

 

  1. Meyer-Olson D, Shoukry NH, Brady KW, et al. Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape. J Exp Med. 2004;200(3):307-319. doi: 10.1084/jem.20040638

 

  1. Yoshizawa K, Ota M, Katsuyama Y, et al. T cell repertoire in the liver of patients with autoimmune hepatitis. Hum Immunol. 1999;60(9):806-815. doi: 10.1016/S0198-8859(99)00058-0

 

  1. Briney B, Inderbitzin A, Joyce C, Burton DR. Commonality despite exceptional diversity in the baseline human antibody repertoire. Nature. 2019;566(7744):393-397. doi: 10.1038/s41586-019-0879-y

 

  1. Soto C, Bombardi RG, Branchizio A, et al. High frequency of shared clonotypes in human B cell receptor repertoires. Nature. 2019;566(7744):398-402. doi: 10.1038/s41586-019-0934-8

 

  1. Soto C, Bombardi RG, Kozhevnikov M, et al. High frequency of shared clonotypes in human T cell receptor repertoires. Cell Rep. 2020;32(2):107882. doi: 10.1016/j.celrep.2020.107882

 

  1. Shugay M, Bolotin DA, Putintseva EV, Pogorelyy MV, Mamedov IZ, Chudakov DM. Huge overlap of individual TCR beta repertoires. Front Immunol. 2013;4:466. doi: 10.3389/fimmu.2013.00466

 

  1. Cibotti R, Cabaniols JP, Pannetier C, et al. Public and private V beta T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice. J Exp Med. 1994;180(3):861-872. doi: 10.1084/jem.180.3.861

 

  1. Price DA, Asher TE, Wilson NA, et al. Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection. J Exp Med. 2009;206(4):923-936. doi: 10.1084/jem.20081127
Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing