Original ArticlesIdentification of Novel Serum Autoantibodies for Differential Diagnosis of Autoimmune Pancreatitis and Pancreatic Ductal AdenocarcinomaFelix, Klaus PhD; Hauck, Oliver PhD; Schnölzer, Martina PhD; Kempf, Tore PhD; Warnken, Uwe PhD; Schneider, Kathrin BA; Bergmann, Frank MD; Fritz, Stefan MD; Werner, Jens MDAuthor Information From the *Department of General Surgery, University of Heidelberg, Heidelberg; †Department of Plant Biochemistry, Dahlem Centre of Plant Sciences, Freie Universität Berlin, Berlin; ‡Functional Proteome Analysis, German Cancer Research Center (DKFZ); and §Institute of Pathology, University of Heidelberg, Heidelberg and ∥Department of General-, Visceral-, Transplantations-, Vascular- and Thorax-Surgery, Ludwig Maximilian University of Munich, Munich, Germany. Received for publication June 5, 2015; accepted February 12, 2016. Address correspondence to: Klaus Felix, PhD, Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany (e-mail: [email protected]). The authors declare no conflict of interest. Pancreas: October 2016 - Volume 45 - Issue 9 - p 1309-1319 doi: 10.1097/MPA.0000000000000647 Buy Metrics Abstract Objectives The lack of specific biochemical markers is a major drawback for the diagnosis of autoimmune pancreatitis (AIP). The aims were to characterize the autoantibody profiles in AIP and pancreatic ductal adenocarcinoma (PDAC) and to identify circulating autoantibodies that could be diagnostic markers differentiating PDAC and the AIP subtypes. Methods Tissue lysates obtained from the resected pancreas of patients with AIP and patients with PDAC were separated by 2-dimensional polyacrylamide gel electrophoresis subsequently immunoblotted with autologous sera. The immunoreactive spots were subjected to nanoscale liquid chromatography–electrospray ionization tandem mass spectrometry to identify serum autoantibodies to tissue-derived autoantigens associated with AIP and PDAC. Autoantibody concentrations for selected autoantigens were assessed by enzyme-linked immunosorbent assays. Results A total of 115 immunoreactive spots were identified by 2-dimensional polyacrylamide gel electrophoresis/immunobloting. Nanoscale liquid chromatography–electrospray ionization tandem mass spectrometry–based analysis revealed 68 autoantigens in AIP, 26 in PDAC, and 21 present in both diseases. Assessment of 13 selected AIP autoantibody serum levels revealed that 7 of them had significantly higher titers in AIP versus PDAC. IgG-directed against transaldolase could significantly differentiate between the 2 AIP subtypes. Conclusions The novel panel of AIP autoantibodies is promising to supplement the predictive tests for AIP of the currently known autoantigens and represent a basis for a combined blood test to differentiate AIP from PDAC in the future. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.