Abstract
Type 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glycopeptides from populations in Asia were found to be isobaric ions when using LC-MS/MS as an analytical tool. In this study, an analytical workflow that coupled affinity purification and stable isotope dilution LC-MS/MS was developed to dissect IgG4 glycosylation profiles for autoimmune pancreatitis. Comparing the IgG4 and glycosylation profiles among healthy controls, patients with pancreatic ductal adenocarcinoma (PDAC), and AIP, the IgG4 glycosylations from the AIP group were found to have more digalactosylation (compared to PDAC) and less monogalactosylation (compared to HC). In addition, higher fucosylation and sialylation profiles were also discovered for the AIP group. The workflow is efficient and selective for IgG4 glycopeptides, and can be used for clinical biosignature discovery.
Highlights
Autoimmune pancreatitis (AIP) is a distinct form of the chronic fibroinflammatory autoimmune disorder of the pancreas [1]
Serum samples from patients with autoimmune pancreatitis (AIP) were pooled, and 10 μL of pooling serum was used for each condition to mimic clinical sample with high concentrations of IgG4
The peak area of the IgG4 surrogate peptide was used for comparison, and the results showed that 20 μL of bead slurry was sufficient to purify IgG4
Summary
Autoimmune pancreatitis (AIP) is a distinct form of the chronic fibroinflammatory autoimmune disorder of the pancreas [1]. AIP can be sub-classified into type 1 and type 2 based on the clinical and pathological features. Type 1 AIP, which represents more than 95% of all AIP cases, is a pancreatic manifestation of systemic immunoglobulin G4related disease (IgG4-RD) characterized by high serum IgG4 concentrations and increased. IgG4-positive plasma cells in the tissues [2,3]. The serum IgG4 level is commonly used as a biomarker for AIP and IgG4-RD, the measurement of the serum IgG subtype suffers from several limitations regarding the diagnosis and assessment of disease activity. 20% of patients with AIP have a serum concentration of IgG4 that is within normal limits [4].
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.