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

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.</p

Combined normal-phase and reversed-phase liquid chromatography/ESI-MS as a tool to determine the molecular diversity of A-type procyanidins in peanut skins

Peanut skins, a byproduct of the peanut butter industry, are a rich source of proanthocyanidins, which might be used in food supplements. Data on the molecular diversity of proanthocyanidins in peanut skins is limited and conflicting with respect to the ratio of double- (A-type) versus single-linked (B-type) flavan-3-ol units. NP- and RP-HPLC-MS were used as tools to analyze the molecular diversity of proanthocyanidins in a 20% (v/v) methanol extract of peanut skins. NP-HPLC was used to prepurify monomeric to pentameric fractions, which were further separated and characterized by RP-HPLC-MS. With this method, 83 different proanthocyanidin molecular species were characterized and quantified. Furthermore, it was possible to determine that A-type procyanidin oligomers were predominant and represented 95.0% (w/w) of the extract. In addition, the position of the A-linkages in 16 trimers and 27 tetramers could be determined, which in this case appeared to occur at all possible positions. The majority of trimers and tetramers with one or more A-linkage always had an A-linkage at the terminal uni