A full repertoire analysis of the BCR heavy chain was performed using GS-FLX/454 and customized bioinformatics algorithms (>10,000 sequences/sample; clones with a frequency ≥0.5% were considered dominant). We found that the most dominant clones within the IgG+ BCRheavy repertoire of the peripheral blood at baseline were IgG4+ only in IAC patients. In all IAC patients, but none of the controls, IgG4+ BCR clones were among the 10 most dominant BCR clones of any immunoglobulin isotype

(IgA, IgD, IgM, and IgG) in blood. Selleck Lapatinib The BCR repertoires of the duodenal papilla comprised the same dominant IgG4+ clones as the paired peripheral blood samples. In all IAC patients, after 4 and 8 weeks of corticosteroid therapy selleck the contribution of these IgG4+ clones to the IgG+ repertoire as well as to total BCR repertoire was marginalized, mirroring sharp declines in serum IgG4 titers and regression of clinical symptoms. Conclusion: The novel finding of highly abundant IgG4+

BCR clones in blood and tissue of patients with active IAC, which disappear upon corticosteroid treatment, suggests that specific B cell responses are pivotal to the pathogenesis of IAC. (HEPATOLOGY 2013 ) Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a common denominator for incompletely understood organ abnormalities associated with IgG4+ B-cell and plasma cell infiltrates and/or elevated serum IgG4 titres.1–6 Although the list of possibly affected organs in IgG4-RD is expanding, the pancreas in the form of autoimmune pancreatitis and biliary tree in the form of IgG4-associated cholangitis (IAC, also known as IgG4-related (sclerosing)

cholangitis) are thus far the most frequently involved localizations. The diagnosis of IgG4-RD is currently made by exclusion of other causes and organ-specific diagnostic criteria, of which the histology, Epothilone B (EPO906, Patupilone) imaging, serology, other organ involvement, and response to steroid therapy (HISORt) criteria that were originally developed for the diagnosis of autoimmune pancreatitis are arguably the most generally applied. Nevertheless, diagnosing IgG4-related disease of the biliary tree is challenging, because this rare disease often mimics malignancies of the bile ducts or pancreatic head as well as primary sclerosing cholangitis (PSC) and forms of secondary sclerosing cholangitis, mainly in terms of symptoms and imaging. The number of IAC patients diagnosed after histological evaluation of surgical specimens, either obtained in diagnostic procedures or during extended resections for suspected malignancies, is far from negligible.7 IgG4-RD derived its name from the elevated serum levels of IgG4 that were found in the original cohorts.