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Background: Autoimmune pancreatitis is a special form of chronic pancreatitis with strong lymphocytic infiltration and two histopathological distinct subtypes, a lymphoplasmacytic sclerosing pancreatitis and idiopathic duct centric pancreatitis. Immunoglobulin G4-associated cholangitis may be present at the time of autoimmune pancreatitis type 1 diagnosis or occur later over the course of the disease. Immunoglobulin G4 is considered reliable but not an ideal marker for diagnosis of autoimmune pancreatitis type 1 with reported sensitivity between 71-81%. It is essential to differentiate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis as the treatment and prognosis of the two diseases are totally different. It was the aim of the study to find a marker for immunoglobulin G4-associated cholangitis that would distinguish it from primary sclerosing cholangitis., Patients and Methods: We performed a retrospective analysis of patients with autoimmune pancreatitis at our outpatient clinic. Patients from the primary sclerosing cholangitis registry were taken as a control group. Blood samples for the measurement of immunoglobulin subclasses were analysed at the time of diagnosis., Results: Patients with autoimmune pancreatitis and immunoglobulin G4-associated cholangitis had higher values of immunoglobulin G2 when compared to autoimmune pancreatitis alone or primary sclerosing cholangitis with a high specificity (97%) and high positive predictive value (91%). In patients with normal or low immunoglobulin G2 or immunoglobulin G4, a high level of immunoglobulin G1 indicated primary sclerosing cholangitis., Conclusion: Immunoglobulin G1 and immunoglobulin G2 can distinguish patients with immunoglobulin G4-associated cholangitis from those with primary sclerosing cholangitis.

Background and Aim: Immunoglobulin subclass G4-related disease (IgG4-RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4-RD and the relationship with disease activity and response to treatment., Methods: We assessed IgG Fc-tail and Fab-arm glycosylation status in patients with IgG4-RD (n = 22), disease controls with primary sclerosing cholangitis (PSC) (n = 22), and healthy controls (n = 22). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index., Results: Immunoglobulin G Fab sialylation was increased in IgG4-RD compared with PSC and healthy control (P = 0.01), with a preferential increase in IgG4-specific Fab sialylation, which was independent of IgG4 Fab-arm exchange. There was a reduction in IgG1-specific Fc bisection and hybrid structures in IgG4-RD (P < 0.01), which recovered upon steroid treatment and correlated with disease activity. Overall, IgG Fc galactosylation was reduced in both IgG4-RD and PSC (P < 0.01), with a preferential reduction in IgG1-specific sialylation and enhancement of IgG4-specific bisection in PSC. IgG4 fucosylation and IgG1/2/3 hybrid structures negatively correlated with complement C3 and C4 levels in IgG4-RD (P < 0.01), but not PSC., Conclusion: We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4-RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) is a biliary tract manifestation of IgG4-related diseases (IgG4-RD); a subgroup of SC defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis. IgG4-SC is clinically characterized by the (a) chronic elevation of cholestatic enzyme levels, (b) significant elevation of serum IgG4 levels, (c) diffuse or segmental narrowing of intra and/or extra hepatic bile ducts with thickening of the bile duct wall in imaging studies, (d) marked lymphoplasmacytic and IgG4-positive plasma cell infiltration and fibrosis in histology, (e) presence of IgG4-RD in other organs, mainly involving autoimmune pancreatitis, and (f) excellent response to corticosteroids. The diagnosis of IgG4-SC is based on a combination of these findings. Although the IgG4-SC diagnosis is different from that of primary sclerosing cholangitis (PSC) or biliary and pancreatic malignancies, it is extremely important to diagnose or suspect IgG4-SC appropriately; as the incorrect diagnosis of PSC or malignant diseases may lead to the progression of fibrosis in patients due to untreated chronic cholestasis, or to unnecessary major surgical resections. Although its etiology remains unclear, recent studies of IgG4-SC have attempted to clarify the roles of the IgG4 molecule and novel autoantibodies detected in patients with IgG4-SC., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

IgG4-related sclerosing cholangitis (IgG4-SC) is characterized by biliary strictures and obstructive jaundice.Elevated levels of serum IgG4 and a multifocal IgG4-rich lymphoplasmacytic infiltration of affected organs are also the characteristics of IgG4-SC. Prednisone is recommended in the initial treatment of IgG4-SC. The differential diagnosis between IgG4-SC and cholangiocarcinoma is not easy. Comprehensively collection of medical history, paying attention to other organs involvement, and getting the pathologic diagnosis are important for diagnosis of this disease. In order to prevent misdiagnosis we should learn more about IgG4-SC. On the other hand, if we can not differentiate IgG4-SC and cholangiocarcinoma, operation may be recommended.