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Primary Sclerosing Cholangitis pp 59–72Cite as

IgG4-Related Sclerosing Cholangitis

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Abstract

IgG4-sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the systemic fibro-inflammatory condition IgG4-related disease. Most commonly it affects men in their seventh decade, but accurate estimates of incidence and prevalence are unknown, particularly in the Western world. The disease often manifests with obstructive jaundice. On imaging its appearance is frequently indistinguishable from primary sclerosing cholangitis or cholangiocarcinoma. Making this distinction is paramount to avoid patients undergoing unnecessary surgical resections for suspected cancer. Although serum IgG4 is raised in the majority of cases, this is not specific to the disease, and diagnosis is based on the combination of this finding together with imaging, histology, involvement of other organs, and responsiveness to steroid therapy. Histologically, disease lesions have a lymphoplasmacytic infiltration, abundant IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Steroids are highly effective at treating IgG4-SC, but half of patients relapse requiring further immunosuppressive therapy. Long term, patients are at risk of irreversible fibrosis, organ dysfunction, and malignancy. The immunological mechanisms of pathogenesis are not yet clear, although there is evidence that both B cells and T cells are involved. This review summarizes the current evidence of IgG4-SC epidemiology and its clinical, radiological, and histological features, treatment, natural history, and pathophysiology.

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References

  1. Aalberse RC, van der Gaag R, van Leeuwen J. Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol. 1983;130(2):722–6.

    CAS  PubMed  Google Scholar 

  2. Akiyama M, Suzuki K, Yamaoka H, Yasuoka H, Takeshita M, Kaneko Y, Kondo H, Kassai Y, Miyazaki T, Morita R, Yoshimura A, Takeuchi T. Number of circulating T follicular helper 2 cells correlates with IgG4 and IL-4 levels and plasmablast numbers in IgG4-related disease. Arthritis Rheumatol. 2015;67(9):2476–81.

    Article  CAS  PubMed  Google Scholar 

  3. Aoki S, Nakazawa T, Ohara H, Sano H, Nakao H, Joh T, Murase T, Eimoto T, Itoh M. Immunohistochemical study of autoimmune pancreatitis using anti-IgG4 antibody and patients' sera. Histopathology. 2005;47(2):147–58.

    Article  CAS  PubMed  Google Scholar 

  4. Aparisi L, Farre A, Gomez-Cambronero L, Martinez J, De Las Heras G, Corts J, Navarro S, Mora J, Lopez-Hoyos M, Sabater L, Ferrandez A, Bautista D, Perez-Mateo M, Mery S, Sastre J. Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut. 2005;54(5):703–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Asada M, Nishio A, Uchida K, Kido M, Ueno S, Uza N, Kiriya K, Inoue S, Kitamura H, Ohashi S, Tamaki H, Fukui T, Matsuura M, Kawasaki K, Nishi T, Watanabe N, Nakase H, Chiba T, Okazaki K. Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis. Pancreas. 2006;33(1):20–6.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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(6):1547–54.

    Article  PubMed  Google Scholar 

  8. Boonstra K, Culver EL, de Buy Wenniger LM, van Heerde MJ, van Erpecum KJ, Poen AC, van Nieuwkerk KM, Spanier BW, Witteman BJ, Tuynman HA, van Geloven N, van Buuren H, Chapman RW, Barnes E, Beuers U, Ponsioen CY. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology. 2014;59(5):1954–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Buechter M, Klein CG, Kloeters C, Schlaak JF, Canbay A, Gerken G, Kahraman A. Tacrolimus as a reasonable alternative in a patient with steroid-dependent and thiopurine-refractory autoimmune pancreatitis with IgG4-associated cholangitis. Z Gastroenterol. 2014;52(6):564–8.

    Article  CAS  PubMed  Google Scholar 

  10. Campochiaro C, Ramirez GA, Bozzolo EP, Lanzillotta M, Berti A, Baldissera E, Dagna L, Praderio L, Scotti R, Tresoldi M, Roveri L, Mariani A, Balzano G, Castoldi R, Doglioni C, Sabbadini MG, Della-Torre E. IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients. Scand J Rheumatol. 2015;23:1–11.

    Google Scholar 

  11. Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone J. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015;74(1):14–8.

    Article  CAS  PubMed  Google Scholar 

  12. Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, Deshpande V, Smyrk TC, Chari S, Stone JH. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015;74(6):1171–7.

    Article  PubMed  Google Scholar 

  13. Culver EL, Vermeulen E, Makuch M, van Leeuwen A, Sadler R, Cargill T, Klenerman P, Aalberse RC, van Ham SM, Barnes E, Rispens T. Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease. Ann Rheum Dis. 2015;74(5):944–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chang MC, Chang YT, Tien YW, Liang PC, Jan IS, Wei SC, Wong JM. T-cell regulatory gene CTLA-4 polymorphism/haplotype association with autoimmune pancreatitis. Clin Chem. 2007;53(9):1700–5.

    Article  CAS  PubMed  Google Scholar 

  15. Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Zhang L, Clain JE, Pearson RK, Petersen BT, Vege SS, Farnell MB. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006;4(8):1010–6.

    Article  PubMed  Google Scholar 

  16. de Buy Wenniger LJ, Culver EL, Beuers U. Exposure to occupational antigens might predispose to IgG4-related disease. Hepatology. 2014;60(4):1453–4.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Della Torre E, Mattoo H, Mahajan VS, Carruthers M, Pillai S, Stone JH. Prevalence of atopy, eosinophilia, and IgE elevation in IgG4-related disease. Allergy. 2014;69(2):269–72.

    Article  CAS  PubMed  Google Scholar 

  18. Deshpande V, Sainani NI, Chung RT, Pratt DS, Mentha G, Rubbia-Brandt L, Lauwers GY. IgG4-associated cholangitis: a comparative histological and immunophenotypic study with primary sclerosing cholangitis on liver biopsy material. Mod Pathol. 2009;22(10):1287–95.

    Article  CAS  PubMed  Google Scholar 

  19. Endo T, Takizawa S, Tanaka S, Takahashi M, Fujii H, Kamisawa T, Kobayashi T. Amylase alpha-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes. Diabetes. 2009;58(3):732–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Esposito I, Born D, Bergmann F, Longerich T, Welsch T, Giese NA, Büchler MW, Kleeff J, Friess H, Schirmacher P. Autoimmune pancreatocholangitis, non-autoimmune pancreatitis and primary sclerosing cholangitis: a comparative morphological and immunological analysis. PLoS One. 2008;3(7):e2539.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–67.

    Article  Google Scholar 

  22. Fernández-Codina A, Martínez-Valle F, Pinilla B, López C, DeTorres I, Solans-Laqué R, Fraile-Rodríguez G, Casanovas-Martínez A, López-Dupla M, Robles-Marhuenda Á, Barragán-González MJ, Cid MC, Prieto-González S, Brito-Zerón P, Cruces-Moreno MT, Fonseca-Aizpuru E, López-Torres M, Gil J, Núñez-Fernández MJ, Pardos-Gea J, Salvador-Cervelló G. IgG4-related disease: results from a multicenter Spanish registry. Medicine (Baltimore). 2015;94(32), e1275.

    Article  CAS  Google Scholar 

  23. Frulloni L, Lunardi C, Simone R, Dolcino M, Scattolini C, Falconi M, Benini L, Vantini I, Corrocher R, Puccetti A. Identification of a novel antibody associated with autoimmune pancreatitis. N Engl J Med. 2009;361(22):2135–42.

    Article  CAS  PubMed  Google Scholar 

  24. Futei Y, Amagai M, Ishii K, Kuroda-Kinoshita K, Ohya K, Nishikawa T. Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus. J Dermatol Sci. 2001;26(1):55–61.

    Article  CAS  PubMed  Google Scholar 

  25. Gardner CS, Bashir MR, Marin D, Nelson RC, Choudhury KR, Ho LM. Diagnostic performance of imaging criteria for distinguishing autoimmune cholangiopathy from primary sclerosing cholangitis and bile duct malignancy. Abdom Imaging. 2015;40(8):3052–61.

    Article  PubMed  Google Scholar 

  26. Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, Topazian MD, Clain JE, Pearson RK, Petersen BT, Vege SS, Lindor K, Farnell MB. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134(3):706–15.

    Article  PubMed  Google Scholar 

  27. Graham RPD, Smyrk TC, Chari ST, Takahashi N, Zhang L. Isolated IgG4-related sclerosing cholangitis: a report of 9 cases. Hum Pathol. 2014;45(8):1722–9.

    Article  CAS  PubMed  Google Scholar 

  28. Guarneri F, Guarneri C, Benvenga S. Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry? J Cell Mol Med. 2005;9(3):741–4.

    Article  CAS  PubMed  Google Scholar 

  29. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344(10):732–8.

    Article  CAS  PubMed  Google Scholar 

  30. Hart PA, Topazian MD, Witzig TE, Clain JE, Gleeson FC, Klebig RR, Levy MJ, Pearson RK, Petersen BT, Smyrk TC, Sugumar A, Takahashi N, Vege SS, Chari ST. Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience. Gut. 2013;62(11):1607–15.

    Article  CAS  PubMed  Google Scholar 

  31. Hirano K, Tada M, Isayama H, Yamamoto K, Mizuno S, Yagioka H, Yashima Y, Sasaki T, Kogure H, Togawa O, Arizumi T, Matsubara S, Nakai Y, Sasahira N, Tsujino T, Kawabe T, Omata M. Endoscopic evaluation of factors contributing to intrapancreatic biliary stricture in autoimmune pancreatitis. Gastrointest Endosc. 2010;71(1):85–90.

    Article  PubMed  Google Scholar 

  32. Huggett MT, Culver EL, Kumar M, Hurst JM, Rodriguez-Justo M, Chapman MH, Johnson GJ, Pereira SP, Chapman RW, Webster GJ, Barnes E. 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):1675–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Huijbers MG, Zhang W, Klooster R, Niks EH, Friese MB, Straasheijm KR, Thijssen PE, Vrolijk H, Plomp JJ, Vogels P, Losen M, Van der Maarel SM, Burden SJ, Verschuuren JJ. MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4. Proc Natl Acad Sci USA. 2013;110(51):20783–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Inoue D, Yoshida K, Yoneda N, Ozaki K, Matsubara T, Nagai K, Okumura K, Toshima F, Toyama J, Minami T, Matsui O, Gabata T, Zen Y. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 2015;94(15):e680.

    Article  CAS  Google Scholar 

  35. Itoh S, Nagasaka T, Suzuki K, Satake H, Ota T, Naganawa S. Lymphoplasmacytic sclerosing cholangitis: assessment of clinical, CT, and pathological findings. Clin Radiol. 2009;64(11):1104–14.

    Article  CAS  PubMed  Google Scholar 

  36. Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol. 1998;160(7):3555–61.

    CAS  PubMed  Google Scholar 

  37. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, Okamoto A, Egawa N, Nakajima H. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38(10):982–4.

    Article  CAS  PubMed  Google Scholar 

  38. Kamisawa T, Anjiki H, Egawa N, Kubota N. Allergic manifestations in autoimmune pancreatitis. Eur J Gastroenterol Hepatol. 2009;21(10):1136–9.

    Article  PubMed  Google Scholar 

  39. Kamisawa T, Shimosegawa T, Okazaki K, Nishino T, Watanabe H, Kanno A, Okumura F, Nishikawa T, Kobayashi K, Ichiya T, Takatori H, Yamakita K, Kubota K, Hamano H, Okamura K, Hirano K, Ito T, Ko SB, Omata M. Standard steroid treatment for autoimmune pancreatitis. Gut. 2009;58(11):1504–7.

    Article  CAS  PubMed  Google Scholar 

  40. Kamisawa T, Okazaki K, Kawa S, Ito T, Inui K, Irie H, Nishino T, Notohara K, Nishimori I, Tanaka S, Nishiyama T, Suda K, Shiratori K, Tanaka M, Shimosegawa T, Working Committee of the Japan Pancreas Society and the Research Committee for Intractable Pancreatic Disease supported by the Ministry of Health, Labour and Welfare of Japan. Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis. J Gastroenterol. 2014;49(6):961–70.

    Article  CAS  PubMed  Google Scholar 

  41. Kanari H, Kagami S, Kashiwakuma D, Oya Y, Furuta S, Ikeda K, Suto A, Suzuki K, Hirose K, Watanabe N, Okamoto Y, Yamamoto S, Iwamoto I, Nakajima H. Role of Th2 cells in IgG4-related lacrimal gland enlargement. Int Arch Allergy Immunol. 2010;152 Suppl 1:47–53.

    Article  CAS  PubMed  Google Scholar 

  42. Kanno A, Nishimori I, Masamune A, Kikuta K, Hirota M, Kuriyama S, Tsuji I, Shimosegawa T, Research Committee on Intractable Diseases of Pancreas. Nationwide epidemiological survey of autoimmune pancreatitis in Japan. Pancreas. 2012;41(6):835–9.

    Article  PubMed  Google Scholar 

  43. Kanno A, Masamune A, Okazaki K, Kamisawa T, Kawa S, Nishimori I, Tsuji I, Shimosegawa T, Research Committee of Intractable Diseases of the Pancreas. Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2011. Pancreas. 2015;44(4):535–9.

    Article  PubMed  Google Scholar 

  44. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, Nakayama K, Tokutake Y, Katsuyama Y, Saito S, Hasebe O, Kiyosawa K. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002;122(5):1264–9.

    Article  PubMed  Google Scholar 

  45. Khosroshahi A, Bloch DB, Deshpande V, Stone JH. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum. 2010;62(6):1755–62.

    Article  CAS  PubMed  Google Scholar 

  46. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore). 2012;91(1):57–66.

    Article  CAS  Google Scholar 

  47. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Löhr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH, Second International Symposium on IgG4-Related Disease. International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol. 2015;67(7):1688–99.

    Article  CAS  PubMed  Google Scholar 

  48. Kojima E, Kimura K, Noda Y, Kobayashi G, Itoh K, Fujita N. Autoimmune pancreatitis and multiple bile duct strictures treated effectively with steroid. J Gastroenterol. 2003;38(6):603–7.

    PubMed  Google Scholar 

  49. Koyabu M, Uchida K, Miyoshi H, Sakaguchi Y, Fukui T, Ikeda H, Takaoka M, Hirohara J, Nishio A, Uemura Y, Uemoto S, Okazaki K. Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases. J Gastroenterol. 2010;45(7):732–41.

    Article  CAS  PubMed  Google Scholar 

  50. Koyama R, Imamura T, Okuda C, Sakamoto N, Honjo H, Takeuchi K. Ultrasonographic imaging of bile duct lesions in autoimmune pancreatitis. Pancreas. 2008;37(3):259–64.

    Article  PubMed  Google Scholar 

  51. Kusuda T, Uchida K, Miyoshi H, Koyabu M, Satoi S, Takaoka M, Shikata N, Uemura Y, Okazaki K. Involvement of inducible costimulator- and interleukin 10-positive regulatory T cells in the development of IgG4-related autoimmune pancreatitis. Pancreas. 2011;40(7):1120–30.

    Article  CAS  PubMed  Google Scholar 

  52. Löhr JM, Faissner R, Koczan D, Bewerunge P, Bassi C, Brors B, Eils R, Frulloni L, Funk A, Halangk W, Jesenofsky R, Kaderali L, Kleeff J, Krüger B, Lerch MM, Lösel R, Magnani M, Neumaier M, Nittka S, Sahin-Tóth M, Sänger J, Serafini S, Schnölzer M, Thierse HJ, Wandschneider S, Zamboni G, Klöppel G. Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process. Am J Gastroenterol. 2010;105(9):2060–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Lin W, Lu S, Chen H, Wu Q, Fei Y, Li M, Zhang X, Tian X, Zheng W, Leng X, Xu D, Wang Q, Shen M, Wang L, Li J, Wu D, Zhao L, Wu C, Yang Y, Peng L, Zhou J, Wang Y, Sha Y, Huang X, Jiao Y, Zeng X, Shi Q, Li P, Zhang S, Hu C, Deng C, Li Y, Zhang S, Liu J, Su J, Hou Y, Jiang Y, You X, Zhang H, Yan L, Zhang W, Zhao Y, Zeng X, Zhang F, Lipsky PE. Clinical characteristics of immunoglobulin G4-related disease: a prospective study of 118 Chinese patients. Rheumatology (Oxford). 2015;54(11):1982–90.

    Article  Google Scholar 

  54. de Buy Wenniger LJ M, Doorenspleet ME, Klarenbeek PL, Verheij J, Baas F, Elferink RP, Tak PP, de Vries N, Beuers U. Immunoglobulin G4+ clones identified by next-generation sequencing dominate the B cell receptor repertoire in immunoglobulin G4 associated cholangitis. Hepatology. 2013;57(6):2390–8.

    Article  CAS  Google Scholar 

  55. Maritati F, Corradi D, Versari A, Casali M, Urban ML, Buzio C, Vaglio A. Rituximab therapy for chronic periaortitis. Ann Rheum Dis. 2012;71(7):1262–4.

    Article  CAS  PubMed  Google Scholar 

  56. Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, Deshpande V, Stone JH, Pillai S. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol. 2014;134(3):679–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mattoo H, Della-Torre E, Mahajan VS, Stone JH, Pillai S. Circulating Th2 memory cells in IgG4-related disease are restricted to a defined subset of subjects with atopy. Allergy. 2014;69(3):399–402.

    Article  CAS  PubMed  Google Scholar 

  58. Mendes FD, Jorgensen R, Keach J, Katzmann JA, Smyrk T, Donlinger J, Chari S, Lindor KD. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006;101(9):2070–5.

    Article  CAS  PubMed  Google Scholar 

  59. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011;34(1):108–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Müller T, Beutler C, Picó AH, Otten M, Dürr A, Al-Abadi H, Guckelberger O, Meyer Zum Büschenfelde D, Jöhrens K, Volkmann M, Lankisch T, Voigtländer T, Anders M, Shibolet O, Jefferson DM, Podolsky DK, Fischer A, Veltzke-Schlieker W, Adler A, Baumgart DC, Sturm A, Wiedenmann B, Schott E, Berg T. Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier. Gastroenterology. 2013;144(5):1116–28.

    Article  PubMed  CAS  Google Scholar 

  61. Miyoshi H, Uchida K, Taniguchi T, Yazumi S, Matsushita M, Takaoka M, Okazaki K. Circulating naïve and CD4 + CD25 high regulatory T cells in patients with autoimmune pancreatitis. Pancreas. 2008;36(2):133–40.

    Article  CAS  PubMed  Google Scholar 

  62. Naitoh I, Nakazawa T, Ohara H, Andoh T, Hayashi K, Tanaka H, Okumura F, Takahashi S, Joh T. Endoscopic transpapillary intraductal ultrasonography and biopsy in the diagnosis of IgG4-related sclerosing cholangitis. J Gastroenterol. 2009;44(11):1147–55.

    Article  PubMed  Google Scholar 

  63. Naitoh I, Zen Y, Nakazawa T, Ando T, Hayashi K, Okumura F, Miyabe K, Yoshida M, Nojiri S, Kanematsu T, Ohara H, Joh T. Small bile duct involvement in IgG4-related sclerosing cholangitis: liver biopsy and cholangiography correlation. J Gastroenterol. 2011;46(2):269–76.

    Article  CAS  PubMed  Google Scholar 

  64. Nakanuma Y, Zen Y. Pathology and immunopathology of immunoglobulin G4-related sclerosing cholangitis: the latest addition to the sclerosing cholangitis family. Hepatol Res. 2007;37 Suppl 3:S478–86.

    Article  CAS  PubMed  Google Scholar 

  65. Nakazawa T, Ohara H, Sano H, Aoki S, Kobayashi S, Okamoto T, Imai H, Nomura T, Joh T, Itoh M. Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc. 2004;60(6):937–44.

    Article  PubMed  Google Scholar 

  66. Nakazawa T, Ohara H, Sano H, Ando T, Joh T. Schematic classification of sclerosing cholangitis with autoimmune pancreatitis by cholangiography. Pancreas. 2006;32(2):229.

    Article  PubMed  Google Scholar 

  67. Nishino T, Toki F, Oyama H, Oi I, Kobayashi M, Takasaki K, Shiratori K. Biliary tract involvement in autoimmune pancreatitis. Pancreas. 2005;30(1):76–82.

    PubMed  Google Scholar 

  68. Ohara H, Okazaki K, Tsubouchi H, Inui K, Kawa S, Kamisawa T, Tazuma S, Uchida K, Hirano K, Yoshida H, Nishino T, Ko SB, Mizuno N, Hamano H, Kanno A, Notohara K, Hasebe O, Nakazawa T, Nakanuma Y, Takikawa H, Research Committee of IgG4-related Diseases; Research Committee of Intractable Diseases of Liver and Biliary Tract; Ministry of Health, Labor and Welfare, Japan; Japan Biliary Association. Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012. J Hepatobiliary Pancreat Sci. 2012;19(5):536–42.

    Article  PubMed  Google Scholar 

  69. Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M, Matsushima Y, Katamura K, Ohmori K, Chiba T. Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 2000;118(3):573–81.

    Article  CAS  PubMed  Google Scholar 

  70. Oseini AM, Chaiteerakij R, Shire AM, Ghazale A, Kaiya J, Moser CD, Aderca I, Mettler TA, Therneau TM, Zhang L, Takahashi N, Chari ST, Roberts LR. Utility of serum immunoglobulin G4 in distinguishing immunoglobulin G4-associated cholangitis from cholangiocarcinoma. Hepatology. 2011;54(3):940–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Park DH, Kim MH, Oh HB, Kwon OJ, Choi YJ, Lee SS, Lee TY, Seo DW, Lee SK. Substitution of aspartic acid at position 57 of the DQbeta1 affects relapse of autoimmune pancreatitis. Gastroenterology. 2008;134(2):440–6.

    Article  CAS  PubMed  Google Scholar 

  72. Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G, de Waal Malefyt R, de Vries JE. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci U S A. 1993;90(8):3730–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Saito Y, Kagami S, Kawashima S, Takahashi K, Ikeda K, Hirose K, Oshitari T, Yamamoto S, Okamoto Y, Nakajima H. Roles of CRTH2+ CD4+ T cells in immunoglobulin G4-related lacrimal gland enlargement. Int Arch Allergy Immunol. 2012;158 Suppl 1:42–6.

    Article  CAS  PubMed  Google Scholar 

  74. Seleznik GM, Reding T, Romrig F, Saito Y, Mildner A, Segerer S, Sun LK, Regenass S, Lech M, Anders HJ, McHugh D, Kumagi T, Hiasa Y, Lackner C, Haybaeck J, Angst E, Perren A, Balmer ML, Slack E, MacPherson A, Manz MG, Weber A, Browning JL, Arkan MC, Rülicke T, Aguzzi A, Prinz M, Graf R, Heikenwalder M. Lymphotoxin β receptor signaling promotes development of autoimmune pancreatitis. Gastroenterology. 2012;143(5):1361–74.

    Article  CAS  PubMed  Google Scholar 

  75. Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Klöppel G, Lerch MM, Löhr M, Notohara K, Okazaki K, Schneider A, Zhang L, International Association of Pancreatology. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40(3):352–8.

    Article  PubMed  Google Scholar 

  76. Sah RP, Chari ST. Serologic issues in IgG4-related systemic disease and autoimmune pancreatitis. Curr Opin Rheumatol. 2011;23(1):108–13.

    Article  CAS  PubMed  Google Scholar 

  77. Sandanayake NS, Church NI, Chapman MH, Johnson GJ, Dhar DK, Amin Z, Deheragoda MG, Novelli M, Winstanley A, Rodriguez-Justo M, Hatfield AR, Pereira SP, Webster GJ. Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2009;7(10):1089–96.

    Article  CAS  PubMed  Google Scholar 

  78. Satoguina JS, Weyand E, Larbi J, Hoerauf A. T regulatory-1 cells induce IgG4 production by B cells: role of IL-10. J Immunol. 2005;174(8):4718–26.

    Article  CAS  PubMed  Google Scholar 

  79. Takeuchi M, Sato Y, Ohno K, Tanaka S, Takata K, Gion Y, Orita Y, Ito T, Tachibana T, Yoshino T. T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease. Mod Pathol. 2014;27(8):1126–36.

    Article  CAS  PubMed  Google Scholar 

  80. Takeuchi M, Ohno K, Takata K, Gion Y, Tachibana T, Orita Y, Yoshino T, Sato Y. Interleukin 13-positive mast cells are increased in immunoglobulin G4-related sialadenitis. Sci Rep. 2015;5:7696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Takikawa H, Takamori Y, Tanaka A, Kurihara H, Nakanuma Y. Analysis of 388 cases of primary sclerosing cholangitis in Japan; Presence of a subgroup without pancreatic involvement in older patients. Hepatol Res. 2004;29(3):153–9.

    Article  PubMed  Google Scholar 

  82. Takizawa S, Endo T, Wanjia X, Tanaka S, Takahashi M, Kobayashi T. HSP 10 is a new autoantigen in both autoimmune pancreatitis and fulminant type 1 diabetes. Biochem Biophys Res Commun. 2009;386(1):192–6.

    Article  CAS  PubMed  Google Scholar 

  83. Tanaka A, Moriyama M, Nakashima H, Miyake K, Hayashida JN, Maehara T, Shinozaki S, Kubo Y, Nakamura S. Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease. Arthritis Rheum. 2012;64(1):254–63.

    Article  CAS  PubMed  Google Scholar 

  84. Tanaka A, Tazuma S, Okazaki K, Tsubouchi H, Inui K, Takikawa H. Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing cholangitis in Japan. J Hepatobiliary Pancreat Sci. 2014;21(1):43–50.

    Article  PubMed  Google Scholar 

  85. 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(3):536–43.

    Article  PubMed  Google Scholar 

  86. Topazian M, Witzig TE, Smyrk TC, Pulido JS, Levy MJ, Kamath PS, Chari ST. Rituximab therapy for refractory biliary strictures in immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2008;6(3):364–6.

    Article  CAS  PubMed  Google Scholar 

  87. Tsuboi H, Matsuo N, Iizuka M, Tsuzuki S, Kondo Y, Tanaka A, Moriyama M, Matsumoto I, Nakamura S, Sumida T. Analysis of IgG4 class switch-related molecules in IgG4-related disease. Arthritis Res Ther. 2012;14(4):R171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Umemura T, Ota M, Hamano H, Katsuyama Y, Kiyosawa K, Kawa S. Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut. 2006;55(9):1367–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Umemura T, Zen Y, Hamano H, Kawa S, Nakanuma Y, Kiyosawa K. Immunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology. 2007;46(2):463–71.

    Article  CAS  PubMed  Google Scholar 

  90. Umemura T, Ota M, Hamano H, Katsuyama Y, Muraki T, Arakura N, Kawa S, Kiyosawa K. Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients. Am J Gastroenterol. 2008;103(3):588–94.

    Article  CAS  PubMed  Google Scholar 

  91. van der Neut KM, Schuurman J, Losen M, Bleeker WK, Martínez-Martínez P, Vermeulen E, den Bleker TH, Wiegman L, Vink T, Aarden LA, De Baets MH, van de Winkel JG, Aalberse RC, Parren PW. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science. 2007;317(5844):1554–7.

    Article  CAS  Google Scholar 

  92. van der Zee JS, van Swieten P, Aalberse RC. Inhibition of complement activation by IgG4 antibodies. Clin Exp Immunol. 1986;64(2):415–22.

    PubMed  PubMed Central  Google Scholar 

  93. Vosskuhl K, Negm AA, Framke T, Weismüller T, Manns MP, Wedemeyer H, Plentz RR, Wedemeyer J, Lankisch TO. Measurement of IgG4 in bile: a new approach for the diagnosis of IgG4-associated cholangiopathy. Endoscopy. 2012;44(1):48–52.

    Article  CAS  PubMed  Google Scholar 

  94. Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, Stone JH. IgG4-related disease: clinical and laboratory features in one hundred twenty-five patients. Arthritis Rheumatol. 2015;67(9):2466–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Wallace ZS, Mattoo H, Carruthers M, Mahajan VS, Della Torre E, Lee H, Kulikova M, Deshpande V, Pillai S, Stone JH. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis. 2015;74(1):190–5.

    Article  CAS  PubMed  Google Scholar 

  96. Waldram R, Tsantoulas D, Kopelman H, Williams R. Chronic pancreatitis, sclerosing cholangitis and sicca complex in two siblings. Lancet. 1975;305(7906):550–2.

    Article  Google Scholar 

  97. Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40(7):1561–8.

    Article  CAS  PubMed  Google Scholar 

  98. Zhang L, Guo L, Huang Y, Wang T, Shi X, Chang H, Yao W, Huang X. Allergic diseases, immunoglobulin E, and autoimmune pancreatitis: a retrospective study of 22 patients. Chin Med J (Engl). 2014;127(23):4104–9.

    Google Scholar 

  99. Zen Y, Harada K, Sasaki M, Sato Y, Tsuneyama K, Haratake J, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Morimoto H, Miwa A, Uchiyama A, Portmann BC, Nakanuma Y. IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated cholangitis: do they belong to a spectrum of sclerosing pancreatitis? Am J Surg Pathol. 2004;28(9):1193–203.

    Article  PubMed  Google Scholar 

  100. 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(8):884–94.

    Article  PubMed  Google Scholar 

  101. Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, Nakanuma Y. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007;45(6):1538–46.

    Article  CAS  PubMed  Google Scholar 

  102. Zen Y, Liberal R, Nakanuma Y, Heaton N, Portmann B. Possible involvement of CCL1-CCR8 interaction in lymphocytic recruitment in IgG4-related sclerosing cholangitis. J Hepatol. 2013;59(5):1059–64.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK

    Tamsin Cargill MBBS, BSc(Hons), MRCP & Emma L. Culver MBChB, BSc(Hons), MRCP, PhD

  2. Nuffield Department of Medicine, University of Oxford, Oxford, UK

    Tamsin Cargill MBBS, BSc(Hons), MRCP, Emma L. Culver MBChB, BSc(Hons), MRCP, PhD & Roger W. Chapman MD, FRCP, FAASLD

  3. Nuffield Department of Medicine, Translational Gastroenterology Unit, Level 5, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK

    Roger W. Chapman MD, FRCP, FAASLD

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  1. Tamsin Cargill MBBS, BSc(Hons), MRCP
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  2. Emma L. Culver MBChB, BSc(Hons), MRCP, PhD
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  3. Roger W. Chapman MD, FRCP, FAASLD
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Correspondence to Roger W. Chapman MD, FRCP, FAASLD .

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  1. Department of Gastroenterology-Hepatology, University of Colorado, Aurora, Colorado, USA

    Lisa M. Forman

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Cargill, T., Culver, E.L., Chapman, R.W. (2017). IgG4-Related Sclerosing Cholangitis. In: Forman, L. (eds) Primary Sclerosing Cholangitis. Springer, Cham. https://doi.org/10.1007/978-3-319-40908-5_5

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