中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 4
Apr.  2020
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Article Contents

Current status of immunogenetic studies on primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2020.04.050
  • Published Date: 2020-04-20
  • Primary biliary cholangitis( PBC) has the pathological feature of progressive intrahepatic cholestasis caused by immune-mediated apoptotic necrosis of small biliary epithelial cells,with a risk of progression to bile duct fibrosis,liver cirrhosis,and hepatocellular carcinoma. PBC has immunogenetic characteristics,and the abnormal genetic regulation of immune response in patients with PBC includes abnormal immune response of T and B lymphocytes involving human leukocyte antigen( HLA) and non-HLA genes and taking pyruvate dehydrogenase complex-E2 in mitochondria of intrahepatic small biliary epithelial cells as the antigen. More than 30% of PBC patients have poor response to ursodeoxycholic acid treatment,and therefore,clarifying the mechanism of abnormal immune regulation in PBC has great clinical significance in guiding the immunotherapy for PBC.

     

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  • [1] BEUERS U,GERSHWIN ME,GISH RG,et al. Changing nomenclature for PBC:From ‘cirrhosis’to ‘cholangitis’[J].Hepatology,2015,62(5):1620-1622.
    [2] INVERNIZZI P,RANSOM M,RAYCHAUDHURI S,et al. Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis[J]. Genes Immun,2012,13(6):461-468.
    [3] ZHAO DT,LIAO HY,ZHANG X,et al. Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis[J]. Liver Int,2014,34(2):220-226.
    [4] UMEMURA T,JOSHITA S,ICHIJO T,et al. Human leukocyte antigen class II molecules confer both susceptibility and progression in Japanese patients with primary biliary cirrhosis[J].Hepatology,2012,55(2):506-511.
    [5] LIU JZ,ALMARRI MA,GAFFNEY DJ,et al. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis[J]. Nat Genet,2012,44(10):1137-1141.
    [6] LLEO A,MARZORATI S,ANAYA JM,et al. Primary biliary cholangitis:A comprehensive overview[J]. Hepatol Int,2017,11(6):485-499.
    [7] CHOW IT,JAMES EA,GATES TJ,et al. Differential binding of pyruvate dehydrogenase complex-E2 epitopes by DRB1*08∶01and DRB1*11∶01 Is predicted by their structural motifs and correlates with disease risk[J]. J Immunol,2013,190(9):4516-4524.
    [8] DARLAY R,AYERS KL,MELLS GF,et al. Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis[J]. PLo S Genet,2018,14(12):e1007833.
    [9] WANG C,ZHENG X,JIANG P,et al. Genome-wide association studies of specific antinuclear autoantibody subphenotypes in primary biliary cholangitis[J]. Hepatology,2019,70(1):294-307.
    [10] KAR SP,SELDIN MF,CHEN W,et al. Pathway-based analysis of primary biliary cirrhosis genome-wide association studies[J]. Genes Immun,2013,14(3):179-186.
    [11] WEBB GJ,HIRSCHFIELD GM. Using GWAS to identify genetic predisposition in hepatic autoimmunity[J]. J Autoimmun,2016,66:25-39.
    [12] GULAMHUSEIN AF,JURAN BD,LAZARIDIS KN. Genomewide association studies in primary biliary cirrhosis[J]. Semin Liver Dis,2015,35(4):392-401.
    [13] LI P,LU G,CUI Y,et al. Association of IL12A expression quantitative trait loci(e QTL)with primary biliary cirrhosis in a chinese han population[J]. Medicine(Baltimore),2016,95(19):e3665.
    [14] WASIK U,WUNSCH E,NORMAN GL,et al. Polymorphisms of IL12RB2 may affect the natural history of primary biliary cholangitis:A single centre study[J]. J Immunol Res,2017,2017:2185083.
    [15] JOSHITA S,UMEMURA T,NAKAMURA M,et al. STAT4 gene polymorphisms are associated with susceptibility and ANA status in primary biliary cirrhosis[J]. Dis Markers,2014,7:727393.
    [16] YANG XC,FUJINO M,CAI SJ,et al. Genetic polymorphisms of cytotoxic T-lymphocyte antigen 4 in primary biliary cholangitis:A meta-analysis[J]. J Immunol Res,2017,11:1-12.
    [17] LI Q,WANG B,PAN F,et al. Association between cytotoxic Tlymphocyte antigen 4 gene polymorphisms and primary biliary cirrhosis in Chinese population:Data from a multicenter study[J]. J Gastroenterol Hepatol,2013,28(8):1397-1402.
    [18] ESKANDARI-NASAB E,TAHMASEBI A,HASHEMI M. Meta-analysis:The relationship between CTLA-4+49 A/G polymorphism and primary biliary cirrhosis and type I autoimmune hepatitis[J]. Immunol Invest,2015,44(4):331-348.
    [19] NAKAMURA M,NISHIDA N,KAWASHIMA M,et al. Genomewide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population[J]. Am J Hum Genet,2012,91(4):721-728.
    [20] HITOMI Y,KAWASHIMA M,AIBA Y,et al. Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1[J]. Hum Genet,2015,134(7):737-747.
    [21] SUN Y,IRWANTO A,TOYO-OKA L,et al. Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis,Crohn’s disease and leprosy[J]. Sci Rep,2016,6:31429.
    [22] MELLS GF,FLOYD JA,MORLEY KI,et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis[J]. Nat Genet,2011,43(4):329-332.
    [23] TANAKA A,INVERNIZZI P,OHIRA H,et al. Replicated association of 17q12-21 with susceptibility of primary biliary cirrhosis in a Japanese cohort[J]. Tissue Antigens,2011,78(1):65-68.
    [24] HITOMI Y,KOJIMA K,KAWASHIMA M,et al. Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis[J]. Sci Rep,2017,7(1):2904.
    [25] LI Y,WANG W,TANG L,et al. Chemokine(C-X-C motif)ligand 13 promotes intrahepatic chemokine(C-X-C motif)receptor 5+lymphocyte homing and aberrant B-cell immune responses in primary biliary cirrhosis[J]. Hepatology,2015,61(6):1998-2007.
    [26] QIU F,TANG R,ZUO X,et al. A genome-wide association study identifies six novel risk loci for primary biliary cholangitis[J]. Nat Commun,2017,8:14828.
    [27] HITOMI Y,NAKATANI K,KOJIMA K,et al. NFKB1 and MANBA confer disease susceptibility to primary biliary cholangitis via independent putative primary functional variants[J]. Cell Mol Gastroenterol Hepatol,2019,7(3):515-532.
    [28] CARBONE M,LLEO A,SANDFORD RN,et al. Implications of genome-wide association studies in novel therapeutics in primary biliary cirrhosis[J]. Eur J Immunol,2014,44(4):945-954.
    [29] KAWASHIMA M,HITOMI Y,AIBA Y,et al. Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population[J]. Hum Mol Genet,2017,26(3):650-659.
    [30] XIA ZY,HAN T,MENG HJ. Clinical effect of early-stage immunosuppression combined with ursodeoxycholic acid in treatment of primary biliary cirrhosis[J]. Clin J Med Offic,2020,48(1):97-98,101.(in Chinese)夏志勇,韩涛,孟红军.早期免疫抑制联合熊去氧胆酸治疗原发性胆汁性肝硬化临床疗效[J].临床军医杂志,2020,48(1):97-98,101.
    [31] RAUTIAINEN H,KARKKAINEN P,KARVONEN AL,et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis:A three-year randomized trial[J]. Hepatology,2005,41(4):747-752.
    [32] HIRSCHFIELD GM,GERSHWIN ME,STRAUSS R,et al. Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid:A proof-of-concept study[J]. Hepatology,2016,64(1):189-199.
    [33] BOWLUS CL,YANG GX,LIU CH,et al. Therapeutic trials of biologics in primary biliary cholangitis:An open label study of abatacept and review of the literature[J]. J Autoimmun,2019,101:26-34.
    [34] MYERS RP,SWAIN MG,LEE SS,et al. B-cell depletion with rituximab in patients with primary biliary cirrhosis refractory to ursodeoxycholic acid[J]. Am J Gastroenterol,2013,108(6):933-941.
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