Differential modulation of XBP1 and PERK ER stress pathways in acute pancreatitis

2013 
s / Pancreatolog generationwe examined the antibody concentration and antibody binding of antibodies isolated from patients with pancreatic adenocarcinoma and chronic pancreatitis as well as control patients without malignancies. Materials and methods: Antibody concentrations of IgG, IgM, IgA, and IgE were determined in serum of patients with pancreatic ductal adenocarcinoma (PC; n1⁄450), chronic pancreatitis (CP; n1⁄450) and control patients (C; n1⁄450) by ELISA. Human IgG was purified on Protein A/G columns. Immunoreactivity of isolated IgG was examined with plasmamembrane fractions and methanol fixed cells from the cell lines Panc-1, MiaPaCa-II, BxPc-3, HPAF-II, HEK-293, and HFF-1 as well as a 100 AAMUC1 tandem repeat peptide. Results are expressed as median and lower quartile/upper quartile. Results: IgG concentrations were significantly reduced in patients with pancreatic adenocarcinoma (C 10.90mg/ml 8.88/11.87; CP 7.53mg/ml 6.61/ 9.36, p<0.001; PC 7.65mg/ml 6.65/10.35, p<0.001). Simultaneously, an increase in IgE concentration was detected in patients with CP and PC (C 28.28ng/ml 13.17/60.88; CP 109.10ng/ml 60.03/169.64 p<0.005; PC 69.75ng/ml 25.77/108.77, p<0.005). IgG binding to tumor cell surfaces was reduced for Panc1, HPAF, BxPc3, and HEK293 cell surfaces (HPAF-II C 0.69 0.610.81; CP 0.63 0.54/0.; PC 0.55 0.47/0.64, p<0.001). Analyses of patients developing anti-tumor cell antibodies showed that a small subset of patients develop IgG with immunoreactivity toward several pancreatic cancer cell lines. Conclusion: Patients with pancreatic disorder not only showed reduced overall IgG concentrations but binding to PDAC cell lines was also reduced. Four patients with pronounced immunoreactivity toward pancreatic cancer cell lines could be identified independent of any pancreatic disorder.
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