IgG4+ B-Cell receptor clones distinguish IgG4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies.

Journal article

IgG4-related disease of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies. An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B-cell receptor (BCR) clones determined by nextgeneration sequencing (NGS) accurately distinguish patients with IgG4-associated cholangitis/autoimmune pancreatitis (n=34) from those with primary sclerosing cholangitis (n=17) and biliary/pancreatic malignancies (n=17). A novel, more affordable, widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA-ratio in blood, also achieves excellent diagnostic accuracy (n=125). Moreover, this qPCR-test performed better than serum IgG4 levels in sensitivity (94% versus 86%) and specificity (99% versus 73%), and correlates with treatment response (n=20).

Conclusion: IgG4+ BCR clones and IgG4/IgG RNA-ratiomarkedly improve delineation, early diagnosis and monitoring of IgG4-related disease of the biliary tree and pancreas.

Authors: Doorenspleet, M; Hubers, L; Culver, E; Maillette de Buy Wenniger, L; Klarenbeek, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Hepatology
• Volume: 64
• Issue: 2
• Pages: 501-507
• Publication date: 2016-03-01
• Acceptance date: 2016-03-24
• DOI: 10.1002/hep.28568
• EISSN: 1527-3350
• ISSN: 0270-9139
• Language: English
• Keywords: B-lymphocytes; cholangiopathy; cholangiocarcinoma; cholestasis; IgG4-related disease