The Role of Immunoglobulin G4 in Outcomes of Primary Sclerosing Cholangitis

Overview

Journal J Clin Med

Specialty General Medicine

Date 2024 Jan 11

PMID 38202086

Authors

Miroslav Vujasinovic

Karouk Said

Christina Villard

Jennifer Carlsson

Christopher Poli

Patrick Maisonneuve

J-Matthias Lohr

Affiliations

Soon will be listed here.

Abstract

Introduction: Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease that is characterized by an inflammatory and fibrotic process affecting bile ducts which eventually develops into liver cirrhosis and liver failure. The aim of this study was to investigate serum IgG subclass distribution in patients with PSC and its possible association with PSC outcomes.

Patients And Methods: We performed a retrospective analysis of 181 patients who had been diagnosed with PSC between January 1970 and December 2015 and followed at our outpatient clinic. Their demographic, immunological, and clinical characteristics were recorded and analyzed.

Results: This study included 181 patients with PSC (120 males, 61 females). There was no association between IgGs and the development of autoimmune hepatitis, cirrhosis, cholangiocarcinoma, liver transplantation, inflammatory bowel disease, and colectomy. Patients with elevated IgG4 had statistically significant higher rates of cholangitis ( = 0.02) and endoscopic retrograde cholangiopancreatography (ERCP) ( = 0.009). High IgG4 values were observed in nine patients who underwent ERCP. In these nine patients, on average, IgG4 was evaluated 5 years after ERCP (min 3 days, max 11 years). Subanalysis considering only IgG4 values evaluated before ERCP showed no significant difference but remains significant if we consider IgG4 values after ERCP.

Conclusion: Elevated IgG4 in our study showed a possible association with higher rates of cholangitis and ERCP among patients with primary sclerosing cholangitis. It seems that IgGs may be a useful tool for the prediction of outcomes in patients with PSC. A prospective study is necessary, especially to study the trends of IgGs values during disease as well as the role of possible seroconversion.

Citing Articles

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References

Taghavi S, Majd S, Sianati M, Sepehrimanesh M . Prevalence of IgG-4-associated cholangiopathy based on serum IgG-4 levels in patients with primary sclerosing cholangitis and its relationship with inflammatory bowel disease. Turk J Gastroenterol. 2016; 27(6):547-552. DOI: 10.5152/tjg.2016.16344. View

Alswat K, Al-Harthy N, Mazrani W, Alshumrani G, Jhaveri K, Hirschfield G . The spectrum of sclerosing cholangitis and the relevance of IgG4 elevations in routine practice. Am J Gastroenterol. 2011; 107(1):56-63. DOI: 10.1038/ajg.2011.375. View

Tanaka A, Tazuma S, Nakazawa T, Isayama H, Tsuyuguchi T, Inui K . No negative impact of serum IgG4 levels on clinical outcome in 435 patients with primary sclerosing cholangitis from Japan. J Hepatobiliary Pancreat Sci. 2017; 24(4):217-225. DOI: 10.1002/jhbp.432. View

Mendes F, Jorgensen R, Keach J, Katzmann J, Smyrk T, Donlinger J . Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006; 101(9):2070-5. DOI: 10.1111/j.1572-0241.2006.00772.x. View

Lin G, Li J . IgG subclass serum levels in systemic lupus erythematosus patients. Clin Rheumatol. 2009; 28(11):1315-8. DOI: 10.1007/s10067-009-1224-x. View

Fosby B, Melum E, Bjoro K, Bennet W, Rasmussen A, Andersen I . Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013. Scand J Gastroenterol. 2015; 50(6):797-808. PMC: 4487534. DOI: 10.3109/00365521.2015.1036359. View

Lohr J, Beuers U, Vujasinovic M, Alvaro D, Frokjaer J, Buttgereit F . European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J. 2020; 8(6):637-666. PMC: 7437085. DOI: 10.1177/2050640620934911. View

Manganis C, Chapman R, Culver E . Review of primary sclerosing cholangitis with increased IgG4 levels. World J Gastroenterol. 2020; 26(23):3126-3144. PMC: 7336326. DOI: 10.3748/wjg.v26.i23.3126. View

Parhizkar B, Mohammad Alizadeh A, Asadzadeh Aghdaee H, Malekpour H, Entezari A . Primary sclerosing cholangitis associated with elevated immunoglobulin-g4: a preliminary study. ISRN Gastroenterol. 2012; 2012:325743. PMC: 3439955. DOI: 10.5402/2012/325743. View

10.

Vujasinovic M, Maier P, Maetzel H, Valente R, Pozzi-Mucelli R, Moro C . Immunoglobulin G subtypes-1 and 2 differentiate immunoglobulin G4-associated sclerosing cholangitis from primary sclerosing cholangitis. United European Gastroenterol J. 2020; 8(5):584-593. PMC: 7268946. DOI: 10.1177/2050640620916027. View

11.

Hippchen T, Sauer P, Goppert B, Schirmacher P, Gotthardt D, Weiss K . Association between serum IgG level and clinical course in primary sclerosing cholangitis. BMC Gastroenterol. 2019; 19(1):153. PMC: 6712727. DOI: 10.1186/s12876-019-1075-0. View

12.

. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009; 51(2):237-67. DOI: 10.1016/j.jhep.2009.04.009. View

13.

Boberg K, Egeland T, Schrumpf E . Long-term effect of corticosteroid treatment in primary sclerosing cholangitis patients. Scand J Gastroenterol. 2003; 38(9):991-5. DOI: 10.1080/00365520310005172. View

14.

Navaneethan U, Venkatesh P, Choudhary M, Shen B, Kiran R . Elevated immunoglobulin G4 level is associated with reduced colectomy-free survival in patients with primary sclerosing cholangitis and ulcerative colitis. J Crohns Colitis. 2012; 7(2):e35-41. DOI: 10.1016/j.crohns.2012.04.006. View

15.

Bjornsson E, Chari S, Silveira M, Gossard A, Takahashi N, Smyrk T . Primary sclerosing cholangitis associated with elevated immunoglobulin G4: clinical characteristics and response to therapy. Am J Ther. 2010; 18(3):198-205. DOI: 10.1097/MJT.0b013e3181c9dac6. View

16.

Zheng W, Jiang F, Shan J, Wang Y, Jia Y, Guo Q . Levels of serum IgG subclasses in patients with liver disease: A retrospective study. Exp Ther Med. 2020; 21(1):45. PMC: 7706388. DOI: 10.3892/etm.2020.9476. View

17.

Zhang L, Lewis J, Abraham S, Smyrk T, Leung S, Chari S . IgG4+ plasma cell infiltrates in liver explants with primary sclerosing cholangitis. Am J Surg Pathol. 2009; 34(1):88-94. DOI: 10.1097/PAS.0b013e3181c6c09a. View

18.

Lohr J, Vujasinovic M, Rosendahl J, Stone J, Beuers U . IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol. 2021; 19(3):185-197. DOI: 10.1038/s41575-021-00529-y. View

19.

Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Loof L, Danielsson A . Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002; 36(3):321-7. DOI: 10.1016/s0168-8278(01)00288-4. View

20.

Zhang H, Li P, Wu D, Xu D, Hou Y, Wang Q . Serum IgG subclasses in autoimmune diseases. Medicine (Baltimore). 2015; 94(2):e387. PMC: 4602543. DOI: 10.1097/MD.0000000000000387. View