IgG4-Related Cholangitis

 

 Permissions and Reprints

Abstract

IgG4-related cholangitis (IRC) is a rare fibroinflammatory disease of the biliary tree and liver and presents the major hepatobiliary manifestation of IgG4-related systemic disease (IgG4-RD). IRC also includes the IgG4-related inflammatory pseudotumor of the liver and IgG4-related cholecystitis. IRC mimics other cholangiopathies such as primary sclerosing cholangitis or cholangiocarcinoma. IRC may be found in 30 to 60% of cases with type 1 autoimmune pancreatitis, the most frequent manifestation of IgG4-RD. The pathogenesis of IRC (and IgG4-RD) is incompletely understood. Genetic predisposition, environmental factors, oligoclonal glucocorticosteroid-sensitive expansion of IgG4⁺ B cells/plasmablasts in blood and affected tissue and blocking autoantibody formation against protective IgG4-specific autoantigens such as annexin A11 and laminin 511-E8 with impaired protection of biliary epithelia against toxic bile acids have been described in IRC. Specific T cell subtypes are involved in the inflammatory process. The diagnosis of IRC is made according to HISORt criteria comprising histopathology, imaging, serology, other organ manifestations, and response to therapy. Treatment of IRC aiming to prevent organ failure and improve symptoms includes remission induction with highly effective glucocorticosteroids and long-term maintenance of remission with immunomodulators such as glucocorticosteroid sparing additives or B cell depleting approaches.

Publication History

Article published online:
08 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

• References

• 1 Kersten R, Trampert DC, Herta T. et al. IgG4-related cholangitis - a mimicker of fibrosing and malignant cholangiopathies. J Hepatol 2023; 79 (06) 1502-1523
  CrossrefPubMedSearch in Google Scholar
• 2 Katz G, Stone JH. Clinical perspectives on IgG4-related disease and its classification. Annu Rev Med 2022; 73: 545-562
  PubMedSearch in Google Scholar
• 3 Löhr JM, Vujasinovic M, Rosendahl J, Stone JH, Beuers U. IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol 2022; 19 (03) 185-197
  CrossrefPubMedSearch in Google Scholar
• 4 Trampert DC, van de Graaf SFJ, Jongejan A, Oude Elferink RPJ, Beuers U. Hepatobiliary acid-base homeostasis: insights from analogous secretory epithelia. J Hepatol 2021; 74 (02) 428-441
  PubMedSearch in Google Scholar
• 5 Deshpande V, Zen Y, Chan JK. et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012; 25 (09) 1181-1192
  CrossrefPubMedSearch in Google Scholar
• 6 Tanaka A, Notohara K. Immunoglobulin G4 (IgG4)-related autoimmune hepatitis and IgG4-hepatopathy: a histopathological and clinical perspective. Hepatol Res 2021; 51 (08) 850-859
  PubMedSearch in Google Scholar
• 7 Nakanuma Y, Ishizu Y, Zen Y, Harada K, Umemura T. Histopathology of IgG4-related autoimmune hepatitis and IgG4-related hepatopathy in IgG4-related disease. Semin Liver Dis 2016; 36 (03) 229-241
  PubMedSearch in Google Scholar
• 8 Yokoyama Y, Akutsu N, Numata Y. et al. Immunoglobulin G4-related autoimmune hepatitis simultaneously concomitant with autoimmune pancreatitis: a case report. Clin J Gastroenterol 2021; 14 (06) 1740-1745
  PubMedSearch in Google Scholar
• 9 Hoffmann C. Verschluss der Gallenwege durch Verdickung der Wandungen. Arch Pathol Anat Physiol 1867; 39: 206-215
  PubMedSearch in Google Scholar
• 10 Beuers U, Maillette de Buy Wenniger LJ, Doorenspleet M. et al. IgG4-associated cholangitis. Dig Dis 2014; 32 (05) 605-608
  PubMedSearch in Google Scholar
• 11 Bartholomew LG, Cain JC, Woolner LB, Utz DC, Ferris DO. Sclerosing cholangitis: its possible association with Riedel's struma and fibrous retroperitonitis. Report of two cases. N Engl J Med 1963; 269: 8-12
  PubMedSearch in Google Scholar
• 12 Kazumori H, Ashizawa N, Moriyama N. et al. Primary sclerosing pancreatitis and cholangitis. Int J Pancreatol 1998; 24 (02) 123-127
  PubMedSearch in Google Scholar
• 13 Erkelens GW, Vleggaar FP, Lesterhuis W, van Buuren HR, van der Werf SD. Sclerosing pancreato-cholangitis responsive to steroid therapy. Lancet 1999; 354 (9172) 43-44
  PubMedSearch in Google Scholar
• 14 Kamisawa T, Funata N, Hayashi Y. et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol 2003; 38 (10) 982-984
  CrossrefPubMedSearch in Google Scholar
• 15 Zen Y, Harada K, Sasaki M. et al. IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: do they belong to a spectrum of sclerosing pancreatitis?. Am J Surg Pathol 2004; 28 (09) 1193-1203
  PubMedSearch in Google Scholar
• 16 Björnsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology 2007; 45 (06) 1547-1554
  PubMedSearch in Google Scholar
• 17 Löhr JM, Beuers U, Vujasinovic M. et al; UEG guideline working group. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J 2020; 8 (06) 637-666
  CrossrefPubMedSearch in Google Scholar
• 18 Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M. Primary sclerosing cholangitis. Lancet 2018; 391 (10139): 2547-2559
  CrossrefPubMedSearch in Google Scholar
• 19 Tanaka A, Tazuma S, Okazaki K. et al. Clinical features, response to treatment, and outcomes of IgG4-related sclerosing cholangitis. Clin Gastroenterol Hepatol 2017; 15 (06) 920-926.e3
  PubMedSearch in Google Scholar
• 20 Huggett MT, Culver EL, Kumar M. et al. Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort. Am J Gastroenterol 2014; 109 (10) 1675-1683
  PubMedSearch in Google Scholar
• 21 Ghazale A, Chari ST, Zhang L. et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology 2008; 134 (03) 706-715
  CrossrefPubMedSearch in Google Scholar
• 22 Erdogan D, Kloek JJ, ten Kate FJ. et al. Immunoglobulin G4-related sclerosing cholangitis in patients resected for presumed malignant bile duct strictures. Br J Surg 2008; 95 (06) 727-734
  CrossrefPubMedSearch in Google Scholar
• 23 Roos E, Hubers LM, Coelen RJS. et al. IgG4-associated cholangitis in patients resected for presumed perihilar cholangiocarcinoma: a 30-year tertiary care experience. Am J Gastroenterol 2018; 113 (05) 765-772
  CrossrefPubMedSearch in Google Scholar
• 24 Zen Y, Fujii T, Sato Y, Masuda S, Nakanuma Y. Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Mod Pathol 2007; 20 (08) 884-894
  PubMedSearch in Google Scholar
• 25 Uchida K, Satoi S, Miyoshi H. et al. Inflammatory pseudotumors of the pancreas and liver with infiltration of IgG4-positive plasma cells. Intern Med 2007; 46 (17) 1409-1412
  PubMedSearch in Google Scholar
• 26 Zen Y. The pathology of IgG4-related disease in the bile duct and pancreas. Semin Liver Dis 2016; 36 (03) 242-256
  PubMedSearch in Google Scholar
• 27 Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol 2010; 34 (12) 1812-1819
  PubMedSearch in Google Scholar
• 28 Vlachou PA, Khalili K, Jang HJ, Fischer S, Hirschfield GM, Kim TK. IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. Radiographics 2011; 31 (05) 1379-1402
  CrossrefPubMedSearch in Google Scholar
• 29 Tokala A, Khalili K, Menezes R, Hirschfield G, Jhaveri KS. Comparative MRI analysis of morphologic patterns of bile duct disease in IgG4-related systemic disease versus primary sclerosing cholangitis. AJR Am J Roentgenol 2014; 202 (03) 536-543
  PubMedSearch in Google Scholar
• 30 Nakazawa T, Naitoh I, Hayashi K. et al. Diagnostic criteria for IgG4-related sclerosing cholangitis based on cholangiographic classification. J Gastroenterol 2012; 47 (01) 79-87
  CrossrefPubMedSearch in Google Scholar
• 31 Swensson J, Tirkes T, Tann M, Cui E, Sandrasegaran K. Differentiating IgG4-related sclerosing cholangiopathy from cholangiocarcinoma using CT and MRI: experience from a tertiary referring center. Abdom Radiol (NY) 2019; 44 (06) 2111-2115
  PubMedSearch in Google Scholar
• 32 Naitoh I, Nakazawa T, Ohara H. et al. Endoscopic transpapillary intraductal ultrasonography and biopsy in the diagnosis of IgG4-related sclerosing cholangitis. J Gastroenterol 2009; 44 (11) 1147-1155
  PubMedSearch in Google Scholar
• 33 European Association for the Study of the Liver. EASL clinical practice guidelines on sclerosing cholangitis. J Hepatol 2022; 77 (03) 761-806
  CrossrefPubMedSearch in Google Scholar
• 34 Culver EL, Sadler R, Simpson D. et al. Elevated serum IgG4 levels in diagnosis, treatment response, organ involvement, and relapse in a prospective IgG4-related disease UK cohort. Am J Gastroenterol 2016; 111 (05) 733-743
  CrossrefPubMedSearch in Google Scholar
• 35 Oseini AM, Chaiteerakij R, Shire AM. et al. Utility of serum immunoglobulin G4 in distinguishing immunoglobulin G4-associated cholangitis from cholangiocarcinoma. Hepatology 2011; 54 (03) 940-948
  CrossrefPubMedSearch in Google Scholar
• 36 Boonstra K, Culver EL, de Buy Wenniger LM. et al. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology 2014; 59 (05) 1954-1963
  CrossrefPubMedSearch in Google Scholar
• 37 Hubers LM, Vos H, Schuurman AR. et al. Annexin A11 is targeted by IgG4 and IgG1 autoantibodies in IgG4-related disease. Gut 2018; 67 (04) 728-735
  CrossrefPubMedSearch in Google Scholar
• 38 Tan L, Guan X, Zeng T. et al. The significance of serum IgG₄ and CA19-9, autoantibodies in diagnosis and differential diagnosis of IgG₄-related sclerosing cholangitis. Scand J Gastroenterol 2018; 53 (02) 206-211
  PubMedSearch in Google Scholar
• 39 Maillette de Buy Wenniger LJ, Doorenspleet ME, Klarenbeek PL. et al. Immunoglobulin G4+ clones identified by next-generation sequencing dominate the B cell receptor repertoire in immunoglobulin G4 associated cholangitis. Hepatology 2013; 57 (06) 2390-2398
  PubMedSearch in Google Scholar
• 40 Mattoo H, Mahajan VS, Della-Torre E. et al. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol 2014; 134 (03) 679-687
  CrossrefPubMedSearch in Google Scholar
• 41 Wallace ZS, Mattoo H, Carruthers M. et al. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis 2015; 74 (01) 190-195
  PubMedSearch in Google Scholar
• 42 de Vries E, Tielbeke F, Hubers L. et al. IgG4/IgG RNA ratio does not accurately discriminate IgG4-related disease from pancreatobiliary cancer. JHEP Rep Innov Hepatol 2020; 2 (04) 100116
  PubMedSearch in Google Scholar
• 43 Radford-Smith DE, Selvaraj EA, Peters R. et al. A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis. Liver Int 2022; 42 (06) 1344-1354
  PubMedSearch in Google Scholar
• 44 Prieto J, Banales JM, Medina JF. Primary biliary cholangitis: pathogenic mechanisms. Curr Opin Gastroenterol 2021; 37 (02) 91-98
  PubMedSearch in Google Scholar
• 45 Prieto J, García N, Martí-Climent JM, Peñuelas I, Richter JA, Medina JF. Assessment of biliary bicarbonate secretion in humans by positron emission tomography. Gastroenterology 1999; 117 (01) 167-172
  PubMedSearch in Google Scholar
• 46 Beuers U, Hohenester S, de Buy Wenniger LJ, Kremer AE, Jansen PL, Elferink RP. The biliary HCO(3)(-) umbrella: a unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies. Hepatology 2010; 52 (04) 1489-1496
  CrossrefPubMedSearch in Google Scholar
• 47 Hohenester S, Wenniger LM, Paulusma CC. et al. A biliary HCO_3- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes. Hepatology 2012; 55 (01) 173-183
  CrossrefPubMedSearch in Google Scholar
• 48 Banales JM, Sáez E, Uriz M. et al. Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology 2012; 56 (02) 687-697
  PubMedSearch in Google Scholar
• 49 Herta T, Kersten R, Chang JC. et al. Role of the IgG4-related cholangitis autoantigen annexin A11 in cholangiocyte protection. J Hepatol 2022; 76 (02) 319-331
  PubMedSearch in Google Scholar
• 50 Carruthers MN, Stone JH, Deshpande V, Khosroshahi A. Development of an IgG4-RD responder index. Int J Rheumatol 2012; 2012: 259408
  CrossrefPubMedSearch in Google Scholar
• 51 Wallace ZS, Khosroshahi A, Carruthers MD. et al. An international multispecialty validation study of the IgG4-related disease responder index. Arthritis Care Res (Hoboken) 2018; 70 (11) 1671-1678
  PubMedSearch in Google Scholar
• 52 Ishikawa Y, Terao C. Genetic analysis of IgG4-related disease. Mod Rheumatol 2020; 30 (01) 17-23
  PubMedSearch in Google Scholar
• 53 Terao C, Ota M, Iwasaki T. et al; Japanese IgG4-Related Disease Working Consortium. IgG4-related disease in the Japanese population: a genome-wide association study. Lancet Rheumatol 2019; 1 (01) e14-e22
  PubMedSearch in Google Scholar
• 54 Smith KG, Clatworthy MR. FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat Rev Immunol 2010; 10 (05) 328-343
  PubMedSearch in Google Scholar
• 55 Umemura T, Fujinaga Y, Ashihara N. et al. IL1R1 gene variants associate with disease susceptibility to IgG4-related periaortitis/periarteritis in IgG4-related disease. Gene 2022; 820: 146212
  PubMedSearch in Google Scholar
• 56 Umemura T, Ota M, Hamano H. et al. Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients. Am J Gastroenterol 2008; 103 (03) 588-594
  PubMedSearch in Google Scholar
• 57 de Buy Wenniger LJ, Culver EL, Beuers U. Exposure to occupational antigens might predispose to IgG4-related disease. Hepatology 2014; 60 (04) 1453-1454
  PubMedSearch in Google Scholar
• 58 Hubers LM, Schuurman AR, Buijs J. et al. Blue-collar work is a risk factor for developing IgG4-related disease of the biliary tract and pancreas. JHEP Rep Innov Hepatol 2021; 3 (06) 100385
  PubMedSearch in Google Scholar
• 59 Grasso C, Giacchero F, Crivellari S, Bertolotti M, Maconi A. A review on the role of environmental exposures in IgG4-related diseases. Curr Environ Health Rep 2023; 10 (03) 303-311
  PubMedSearch in Google Scholar
• 60 Wallwork R, Perugino CA, Fu X. et al. The association of smoking with immunoglobulin G4-related disease: a case-control study. Rheumatology (Oxford) 2021; 60 (11) 5310-5317
  PubMedSearch in Google Scholar
• 61 Martín-Nares E, Gamboa-Espíndola M, Hernández-Molina G. Occupational, smoking and biomass fuel exposure in a cohort of Mexican patients with IgG4-related disease. Clin Exp Rheumatol 2024; 42 (12) 2357-2361
  PubMedSearch in Google Scholar
• 62 Hall NE, Rosenman KD. Cancer by industry: analysis of a population-based cancer registry with an emphasis on blue-collar workers. Am J Ind Med 1991; 19 (02) 145-159
  PubMedSearch in Google Scholar
• 63 Liu Q, Li B, Li Y. et al. Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis. Gut 2022; 71 (05) 899-909
  PubMedSearch in Google Scholar
• 64 Kubota K, Kamisawa T, Nakazawa T. et al; Collaborators. Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: based on a Japanese nationwide study. J Gastroenterol Hepatol 2023; 38 (04) 556-564
  PubMedSearch in Google Scholar
• 65 Shah AA, Casciola-Rosen L, Rosen A. Review: cancer-induced autoimmunity in the rheumatic diseases. Arthritis Rheumatol 2015; 67 (02) 317-326
  PubMedSearch in Google Scholar
• 66 Sassano M, Collatuzzo G, Teglia F, Boffetta P. Occupational exposure to diesel exhausts and liver and pancreatic cancers: a systematic review and meta-analysis. Eur J Epidemiol 2024; 39 (03) 241-255
  PubMedSearch in Google Scholar
• 67 McNamee R, Braganza JM, Hogg J, Leck I, Rose P, Cherry NM. Occupational exposure to hydrocarbons and chronic pancreatitis: a case-referent study. Occup Environ Med 1994; 51 (09) 631-637
  PubMedSearch in Google Scholar
• 68 Rispens T, Huijbers MG. The unique properties of IgG4 and its roles in health and disease. Nat Rev Immunol 2023; 23 (11) 763-778
  PubMedSearch in Google Scholar
• 69 Motta RV, Culver EL. IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease. Front Immunol 2024; 15: 1272084
  PubMedSearch in Google Scholar
• 70 Shiokawa M, Kodama Y, Sekiguchi K. et al. Laminin 511 is a target antigen in autoimmune pancreatitis. Sci Transl Med 2018; 10 (453) 10
  PubMedSearch in Google Scholar
• 71 Trampert DC, Kersten R, Tolenaars D, Jongejan A, van de Graaf SFJ, Beuers U. Laminin 511-E8, an autoantigen in IgG4-related cholangitis, contributes to cholangiocyte protection. JHEP Rep Innov Hepatol 2024; 6 (04) 101015
  PubMedSearch in Google Scholar
• 72 Perugino CA, AlSalem SB, Mattoo H. et al. Identification of galectin-3 as an autoantigen in patients with IgG₄-related disease. J Allergy Clin Immunol 2019; 143 (02) 736-745.e6
  PubMedSearch in Google Scholar
• 73 Kersten R, Trampert DC, Hubers LM. et al. Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids. Front Immunol 2024; 14: 1251134
  PubMedSearch in Google Scholar
• 74 Shiokawa M, Kodama Y, Kuriyama K. et al. Pathogenicity of IgG in patients with IgG4-related disease. Gut 2016; 65 (08) 1322-1332
  PubMedSearch in Google Scholar
• 75 Liu H, Perugino CA, Ghebremichael M. et al. Disease severity linked to increase in autoantibody diversity in IgG4-related disease. Arthritis Rheumatol 2020; 72 (04) 687-693
  PubMedSearch in Google Scholar
• 76 Iino S, Sudo T, Niwa T, Fukasawa T, Hidaka H, Niki I. Annexin XI may be involved in Ca²⁺ - or GTP-gammaS-induced insulin secretion in the pancreatic beta-cell. FEBS Lett 2000; 479 (1–2): 46-50
  PubMedSearch in Google Scholar
• 77 Beuers U, Nathanson MH, Isales CM, Boyer JL. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca⁺⁺ mechanisms defective in cholestasis. J Clin Invest 1993; 92 (06) 2984-2993
  PubMedSearch in Google Scholar
• 78 Chang JC, Go S, de Waart DR. et al. Soluble adenylyl cyclase regulates bile salt-induced apoptosis in human cholangiocytes. Hepatology 2016; 64 (02) 522-534
  PubMedSearch in Google Scholar
• 79 van Niekerk J, Kersten R, Beuers U. Role of bile acids and the biliary HCO₃ ^- umbrella in the pathogenesis of primary biliary cholangitis. Clin Liver Dis 2018; 22 (03) 457-479
  PubMedSearch in Google Scholar
• 80 Prieto J, Qian C, García N, Díez J, Medina JF. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Gastroenterology 1993; 105 (02) 572-578
  PubMedSearch in Google Scholar
• 81 Medina JF, Martínez-Ansó Vazquez JJ, Prieto J. Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis. Hepatology 1997; 25 (01) 12-17
  CrossrefPubMedSearch in Google Scholar
• 82 Reich M, Spomer L, Klindt C. et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis. J Hepatol 2021; 75 (03) 634-646
  PubMedSearch in Google Scholar
• 83 Takayama K, Mitani S, Nagamoto Y. et al. Laminin 411 and 511 promote the cholangiocyte differentiation of human induced pluripotent stem cells. Biochem Biophys Res Commun 2016; 474 (01) 91-96
  PubMedSearch in Google Scholar
• 84 Song J, Zhang X, Buscher K. et al. Endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration. Cell Rep 2017; 18 (05) 1256-1269
  PubMedSearch in Google Scholar
• 85 Trampert DC, Kersten R, Nocentini A. et al. Autoantibodies against carbonic anhydrase isoforms inhibit enzymatic function in primary sclerosing cholangitis and IgG4-related cholangitis. Hepatology 2024; 80: S1809
  PubMedSearch in Google Scholar
• 86 Yoshikawa T, Watanabe T, Minaga K, Kamata K, Kudo M. Cytokines produced by innate immune cells in IgG4-related disease. Mod Rheumatol 2019; 29 (02) 219-225
  PubMedSearch in Google Scholar
• 87 Della-Torre E, Lanzillotta M, Doglioni C. Immunology of IgG4-related disease. Clin Exp Immunol 2015; 181 (02) 191-206
  PubMedSearch in Google Scholar
• 88 Yamashina M, Nishio A, Nakayama S. et al. Comparative study on experimental autoimmune pancreatitis and its extrapancreatic involvement in mice. Pancreas 2012; 41 (08) 1255-1262
  PubMedSearch in Google Scholar
• 89 Ishiguro N, Moriyama M, Furusho K. et al. Activated M2 macrophages contribute to the pathogenesis of IgG4-related disease via toll-like receptor 7/interleukin-33 signaling. Arthritis Rheumatol 2020; 72 (01) 166-178
  PubMedSearch in Google Scholar
• 90 Watanabe T, Yamashita K, Arai Y. et al. Chronic fibro-inflammatory responses in autoimmune pancreatitis depend on IFN-α and IL-33 produced by plasmacytoid dendritic cells. J Immunol 2017; 198 (10) 3886-3896
  PubMedSearch in Google Scholar
• 91 Pillai S, Perugino C, Kaneko N. Immune mechanisms of fibrosis and inflammation in IgG4-related disease. Curr Opin Rheumatol 2020; 32 (02) 146-151
  PubMedSearch in Google Scholar
• 92 Zen Y, Fujii T, Harada K. et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology 2007; 45 (06) 1538-1546
  PubMedSearch in Google Scholar
• 93 Akiyama M, Suzuki K, Yasuoka H, Kaneko Y, Yamaoka K, Takeuchi T. Follicular helper T cells in the pathogenesis of IgG4-related disease. Rheumatology (Oxford) 2018; 57 (02) 236-245
  PubMedSearch in Google Scholar
• 94 Akiyama M, Yasuoka H, Yamaoka K. et al. Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease. Arthritis Res Ther 2016; 18: 167
  PubMedSearch in Google Scholar
• 95 Cargill T, Makuch M, Sadler R. et al. Correction: activated T-follicular helper 2 cells are associated with disease activity in IgG4-related sclerosing cholangitis and pancreatitis. Clin Transl Gastroenterol 2019; 10 (07) 1
  CrossrefPubMedSearch in Google Scholar
• 96 Cargill T, Barnes E, Culver EL. Expansion of a novel subset of PD1+CXCR5-CD4+ T peripheral helper cells in IgG4-related disease. Clin Transl Gastroenterol 2020; 11 (01) e00111
  PubMedSearch in Google Scholar
• 97 Mattoo H, Mahajan VS, Maehara T. et al. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease. J Allergy Clin Immunol 2016; 138 (03) 825-838
  PubMedSearch in Google Scholar
• 98 Della-Torre E, Bozzalla-Cassione E, Sciorati C. et al. A CD8α- subset of CD4+SLAMF7+ cytotoxic T cells is expanded in patients with IgG4-related disease and decreases following glucocorticoid treatment. Arthritis Rheumatol 2018; 70 (07) 1133-1143
  PubMedSearch in Google Scholar
• 99 Perugino CA, Kaneko N, Maehara T. et al. CD4⁺ and CD8⁺ cytotoxic T lymphocytes may induce mesenchymal cell apoptosis in IgG₄-related disease. J Allergy Clin Immunol 2021; 147 (01) 368-382
  PubMedSearch in Google Scholar
• 100 Della-Torre E, Feeney E, Deshpande V. et al. B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease. Ann Rheum Dis 2015; 74 (12) 2236-2243
  PubMedSearch in Google Scholar
• 101 Della-Torre E, Rigamonti E, Perugino C. et al. B lymphocytes directly contribute to tissue fibrosis in patients with IgG₄-related disease. J Allergy Clin Immunol 2020; 145 (03) 968-981.e14
  PubMedSearch in Google Scholar
• 102 Heeringa JJ, Karim AF, van Laar JAM. et al. Expansion of blood IgG₄ ⁺ B, T_H2, and regulatory T cells in patients with IgG₄-related disease. J Allergy Clin Immunol 2018; 141 (05) 1831-1843.e10
  PubMedSearch in Google Scholar
• 103 Lanzillotta M, Della-Torre E, Milani R. et al. Increase of circulating memory B cells after glucocorticoid-induced remission identifies patients at risk of IgG4-related disease relapse. Arthritis Res Ther 2018; 20 (01) 222
  PubMedSearch in Google Scholar
• 104 Orozco-Gálvez O, Fernández-Codina A, Lanzillotta M. et al. Development of an algorithm for IgG4-related disease management. Autoimmun Rev 2023; 22 (03) 103273
  PubMedSearch in Google Scholar
• 105 Wu Q, Chang J, Chen H. et al. Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4-related diseases: a preliminary randomized controlled trial. Int J Rheum Dis 2017; 20 (05) 639-646
  PubMedSearch in Google Scholar
• 106 Iguchi T, Takaori K, Mii A. et al. Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease. Mod Pathol 2018; 31 (06) 890-899
  PubMedSearch in Google Scholar
• 107 Lanzillotta M, Della-Torre E, Milani R. et al. Effects of glucocorticoids on B-cell subpopulations in patients with IgG4-related disease. Clin Exp Rheumatol 2019; 37 (3, suppl 118): 159-166
  PubMedSearch in Google Scholar
• 108 Mack CL, Adams D, Assis DN. et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the study of liver diseases. Hepatology 2020; 72 (02) 671-722
  PubMedSearch in Google Scholar
• 109 European Association for the Study of the Liver. EASL clinical practice guidelines: autoimmune hepatitis. J Hepatol 2015; 63 (04) 971-1004
  CrossrefPubMedSearch in Google Scholar
• 110 Omar D, Chen Y, Cong Y, Dong L. Glucocorticoids and steroid sparing medications monotherapies or in combination for IgG4-RD: a systematic review and network meta-analysis. Rheumatology (Oxford) 2020; 59 (04) 718-726
  PubMedSearch in Google Scholar
• 111 Carruthers MN, Topazian MD, Khosroshahi A. et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis 2015; 74 (06) 1171-1177
  CrossrefPubMedSearch in Google Scholar
• 112 Majumder S, Mohapatra S, Lennon RJ. et al. Rituximab maintenance therapy reduces rate of relapse of pancreaticobiliary immunoglobulin G4-related disease. Clin Gastroenterol Hepatol 2018; 16 (12) 1947-1953
  PubMedSearch in Google Scholar
• 113 Stone JH, Khosroshahi A, Zhang W. et al. Inebilizumab for treatment of IgG4-related disease. N Engl J Med 2024; 27 (392) 1168-1177
  PubMedSearch in Google Scholar
• 114 Perugino CA, Wallace ZS, Zack DJ. et al. Evaluation of the safety, efficacy, and mechanism of action of obexelimab for the treatment of patients with IgG4-related disease: an open-label, single-arm, single centre, phase 2 pilot trial. Lancet Rheumatol 2023; 5 (08) e442-e450
  PubMedSearch in Google Scholar
• 115 Harms MH, van Buuren HR, Corpechot C. et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J Hepatol 2019; 71 (02) 357-365
  CrossrefPubMedSearch in Google Scholar
• 116 Beuers U, Trauner M, Jansen P, Poupon R. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol 2015; 62 (01) S25-S37
  CrossrefPubMedSearch in Google Scholar
• 117 Ali AH, Bi Y, Machicado JD. et al. The long-term outcomes of patients with immunoglobulin G4-related sclerosing cholangitis: the Mayo Clinic experience. J Gastroenterol 2020; 55 (11) 1087-1097
  PubMedSearch in Google Scholar
• 118 European Association for the Study of the Liver. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67 (01) 145-172
  CrossrefPubMedSearch in Google Scholar
• 119 Kurita Y, Fujita Y, Sekino Y. et al. IgG4-related sclerosing cholangitis may be a risk factor for cancer. J Hepatobiliary Pancreat Sci 2021; 28 (06) 524-532
  PubMedSearch in Google Scholar
• 120 de Jong IEM, Hunt ML, Chen D. et al. A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia. J Hepatol 2023; 79 (06) 1396-1407
  PubMedSearch in Google Scholar