免疫组库及高通量分析技术在原发性胆汁性胆管炎中的研究进展

赵丹彤; 郭昌龙; 闫惠平

doi:10.3969/j.issn.1001-5256.2017.07.041

免疫组库及高通量分析技术在原发性胆汁性胆管炎中的研究进展

DOI: 10.3969/j.issn.1001-5256.2017.07.041

1. 首都医科大学附属北京佑安医院自身免疫性肝病临床研究中心暨临床检验中心
2. 国家卫生计生委科学技术研究所

基金项目:

国家自然科学基金青年科学基金资助项目(81400609)；北京市医院管理局临床医学发展专项——“扬帆”计划资助项目(ZYLX201711)；

详细信息

中图分类号: R575.7
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出版历程
- 收稿日期: 2017-01-09
- 出版日期: 2017-07-20

Research advances in immune repertoire and high-throughput sequencing in primary biliary cholangitis

Clinical Research Center for Autoimmune Liver Disease & Clinical Laboratory Center, Beijing You An Hospital, Capital Medical University

Research funding:

摘要

摘要: 原发性胆汁性胆管炎（PBC）是一种器官特异性自身免疫性肝脏疾病,发病机制尚不明确。T淋巴细胞受体（TCR）和B淋巴细胞受体（BCR）互补决定区3氨基酸组成和排列顺序呈现高度多样性,构成容量巨大的抗原识别受体库,即免疫组库。采用第二代测序技术结合多重PCR或扩增子救援多重PCR技术研究PBC患者免疫组库特征是近年的研究热点,目前发现PBC存在特异性CD4+T淋巴细胞大量克隆扩增,B淋巴细胞克隆多样性、体细胞高频突变及类别转换现象明显减少,熊去氧胆酸治疗后克隆多样性增加。上述发现有待通过大范围体内和体外试验及不同的免疫组库研究策略进行验证。
- 肝硬化,胆汁性 /
- 免疫组库 /
- 互补决定区 /
- 综述
Abstract: Primary biliary cholangitis (PBC) is an autoimmune liver disease with unclear pathogenesis.The amino acid composition and sequence in the complementarity-determining region 3 of T cell receptor (TCR) and B cell receptor (BCR) are highly diverse, which forms a large antigen recognition receptor repertoire, i.e., immune repertoire.In recent years, second-generation sequencing techniques combined with multiplex PCR or amplicon rescue multiplex PCR have been used to study the features of immune repertoire in PBC patients, and it has been found that PBC patients have clonal expansion of specific CD4~+T lymphocytes, clonal diversity of B lymphocytes, somatic hypermutation, and reduction in class switch, as well as increase in clonal diversity after treatment with ursodeoxycholic acid.These findings need to be confirmed by large-scale in vivo and in vitro studies and different immune repertoire research strategies.
- liver cirrhosis, biliary /
- immunerepertoire /
- complementarity determining regions /
- review

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参考文献(17)

[1]Chinese Society of Hepatology, Chinese Medical Association;Chineses Society of Gastroenterology, Chinese Medical Association;Chinese Society of Infectious Diseases, Chinese Medical Association.Consensus on the diagnosis and management of primary biliary cirrhosis (cholangitis) (2015) [J].J Clin Hepatol, 2015, 31 (12) :1980-1988. (in Chinese) 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会.原发性胆汁性肝硬化 (又名原发性胆汁性胆管炎) 诊断和治疗共识 (2015) [J].临床肝胆病杂志, 2015, 31 (12) :1980-1988.

[2]LINDOR KD, GERSHWIN ME, POUPON R, et al.Primary biliary cirrhosis[J].Hepatology, 2009, 50 (1) :291-308.

[3] BAO JJ, XU QH, ZOU Y, et al.Deep sequencing of the T cell receptor VβCDR3 repertoire of peripheral CD4+T cells in primary biliary cirrhosis[J].Chin J Heptaol, 2015, 23 (8) :580-585. (in Chinese) 鲍俊杰, 徐启桓, 邹勇, 等.高通量测序分析原发性胆汁性肝硬化患者外周血CD4+T细胞受体Vβ链CDR3免疫组库[J].中华肝脏病杂志, 2015, 23 (8) :580-585.

[4]FOREMAN AL, LEMERCIER B, LIM A, et al.VH gene usage and CDR3 analysis of B cell receptor in the peripheral blood of patients with PBC[J].Autoimmunity, 2008, 41 (1) :80-86.

[5]TAN YG, WANG YQ, ZHANG M, et al.Clonal characteristics o circulating B lymphocyte repertoire in primary biliary cholangitis[J].J Immunol, 2016, 197 (5) :1609-1620.

[6]PANNETIER C, COCHET M, DARCHE S, et al.The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments[J].Proc Natl Acad Sci U S A, 1993, 90 (9) :4319-4323.

[7]MARDIS ER.Next-generation DNA sequencing methods[J].Annu Rev Genomics Hum Genet, 2008, 9:387-402.

[8]SHENDURE J, JI H.Next-generation DNA sequencing[J].Nat Biotechnol, 2008, 26 (10) :1135-1145.

[9]FINN JA, CROWE JE Jr.Impact of new sequencing technologies on studies of the human B cell repertoire[J].Curr Opin Immunol, 2013, 25 (5) :613-618.

[10]LINNEMANN C, HEEMSKERK B, KVISTBORG P, et al.Highthroughput identification of antigen-specific TCRs by TCR gene capture[J].Nat Med, 2013, 19 (11) :1534-1541.

[11]WANG C, SANDER CM, YANG Q, et al.High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets[J].Proc Natl Acad Sci U S A, 2010, 107 (4) :1518-1523.

[12]GAO F, LIN E, FENG Y, et al.Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer[J].PLo S One, 2013, 8 (9) :e75294.

[13]GUO CL, DU M, WANG QD, et al.Effect of pregnancy on IGH-CDR3 immunerepertoire in peripheral blood of pregnant women[J].Clin J Fam Plann, 2016, 24 (5) :292-295. (in Chinese) 郭昌龙, 杜蒙, 王启迪, 等.妊娠对孕妇外周血IGH-CDR3免疫组库的影响[J].中国计划生育学杂志, 2016, 24 (5) :292-295.

[14]GUO CL, YU S, WANG QD, et al.The change on immunorepertoire of IGH CDR3in peripheral blood of patients with preeclampsia[J].Clin J Fam Plann, 2016, 24 (3) :160-164. (in Chinese) 郭昌龙, 于松, 王启迪, 等.子痫前期患者外周血IGH-CDR3免疫组库的变化[J].中国计划生育学杂志, 2016, 24 (3) :160-164.

[15]GUO C, WANG Q, CAO X, et al.High-throughput sequencing reveals immunological characteristics of the TRB-/Ig H-CDR3 region of umbilical cord blood[J].J Pediatr, 2016, 176:69-78.

[16]CAO X, WA Q, WANG Q, et al.High throughput sequencing reveals the diversity of TRB-CDR3 repertoire in patients with psoriasis vulgaris[J].Int Immunopharmacol, 2016, 40:487-491.

[17]MICHAELI M, BARAK M, HAZANOV L, et al.Automated analysis of immunoglobulin genes from high-throughput sequencing:life without a template[J].J Clin Bioinforma, 2013, 3 (1) :15.

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