IgG4-related disease of the biliary tract and pancreas Catching a great mimicker

The biliary tract and pancreas are most frequently affected. IgG4-RD is notoriously difficult to distinguish from other biliary/pancreatic diseases, including primary sclerosing cholangitis (PSC) and biliary/pancreatic malignancies. As a consequence, misdiagnosis and incorrect treatments are common.
The first part of this thesis focuses on the diagnostic dilemma in IgG4-RD. In a retrospective study, we showed that a remarkable 15% of the 320 patients that underwent surgery for a presumed malignancy of the extra-hepatic biliary tract in the Amsterdam UMC (location AMC) in the past 30 years, were post-operatively proven to have benign disease and not cancer. Of this group, almost half of the patients showed features of IgG4-RD. Furthermore, we investigated the diagnostic accuracy of the IgG4/IgG RNA ratio among patients with a presumed biliary/pancreatic malignancy in a prospective trial. However, this test was unable to distinguish IgG4-RD from true malignancies.
The second part of this thesis discusses the pathophysiological mechanisms underlying IgG4-RD. We performed a literature study on IgG4 in inflammatory conditions unrelated to IgG4-RD to get a better understanding of its biological properties and its function in disease. Also, we searched for auto-antigens, that may be responsible for the clonally expanded IgG4-producing B cells, which we had identified previously in patients with IgG4-RD. We identified Annexin A11 as the first IgG4-target antigen in a proportion of the patients, while patients with PSC and cholangiocarcinoma did not show reactivity against this antigen. Finally, we could confirm our hypothesis that ‘blue-collar work’ is an independent risk factor for developing biliary/pancreatic IgG4-RD, which may explain the male predominance among patients.