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Open AccessArticle

Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach

1
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
2
Department of Biochemistry, University of Lausanne, 1066 Epalinges-Lausanne, Switzerland
3
Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
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Department of Functional Genomics, DKFZ, 69120 Heidelberg, Germany
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Department of Medical Specialties, Division of Gastroenterology, University Hospital of Geneva, 1205 Geneva, Switzerland
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Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
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Center for Clinical Research and Advanced Medicine Shiga University of Medical Science Seta Tsukinowa-cho, Otsu 520-2192, Japan
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Institute of Medical Biometry and Informatics, University Medical Center Ruprecht-Karls University Heidelberg, 69120 Heidelberg, Germany
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Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2403; https://doi.org/10.3390/ijms21072403
Received: 9 March 2020 / Revised: 27 March 2020 / Accepted: 30 March 2020 / Published: 31 March 2020
(This article belongs to the Special Issue The Immune Landscape in Solid Tumors)
Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients’ sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance. View Full-Text
Keywords: pancreatic cancer; chronic pancreatitis; autoimmune pancreatitis type 1 and type 2; antibodies; microarray protein pancreatic cancer; chronic pancreatitis; autoimmune pancreatitis type 1 and type 2; antibodies; microarray protein
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Ghassem-Zadeh, S.; Hufnagel, K.; Bauer, A.; Frossard, J.-L.; Yoshida, M.; Kutsumi, H.; Acha-Orbea, H.; Neulinger-Muñoz, M.; Vey, J.; Eckert, C.; Strobel, O.; Hoheisel, J.D.; Felix, K. Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach. Int. J. Mol. Sci. 2020, 21, 2403.

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