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

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 determ...

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Autores principales: Ghassem-Zadeh, Sahar, Hufnagel, Katrin, Bauer, Andrea, Frossard, Jean-Louis, Yoshida, Masaru, Kutsumi, Hiromu, Acha-Orbea, Hans, Neulinger-Muñoz, Matthias, Vey, Johannes, Eckert, Christoph, Strobel, Oliver, Hoheisel, Jörg D., Felix, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177860/
https://www.ncbi.nlm.nih.gov/pubmed/32244327
http://dx.doi.org/10.3390/ijms21072403
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author Ghassem-Zadeh, Sahar
Hufnagel, Katrin
Bauer, Andrea
Frossard, Jean-Louis
Yoshida, Masaru
Kutsumi, Hiromu
Acha-Orbea, Hans
Neulinger-Muñoz, Matthias
Vey, Johannes
Eckert, Christoph
Strobel, Oliver
Hoheisel, Jörg D.
Felix, Klaus
author_facet Ghassem-Zadeh, Sahar
Hufnagel, Katrin
Bauer, Andrea
Frossard, Jean-Louis
Yoshida, Masaru
Kutsumi, Hiromu
Acha-Orbea, Hans
Neulinger-Muñoz, Matthias
Vey, Johannes
Eckert, Christoph
Strobel, Oliver
Hoheisel, Jörg D.
Felix, Klaus
author_sort Ghassem-Zadeh, Sahar
collection PubMed
description 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.
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spelling pubmed-71778602020-04-28 Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach Ghassem-Zadeh, Sahar Hufnagel, Katrin Bauer, Andrea Frossard, Jean-Louis Yoshida, Masaru Kutsumi, Hiromu Acha-Orbea, Hans Neulinger-Muñoz, Matthias Vey, Johannes Eckert, Christoph Strobel, Oliver Hoheisel, Jörg D. Felix, Klaus Int J Mol Sci Article 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. MDPI 2020-03-31 /pmc/articles/PMC7177860/ /pubmed/32244327 http://dx.doi.org/10.3390/ijms21072403 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ghassem-Zadeh, Sahar
Hufnagel, Katrin
Bauer, Andrea
Frossard, Jean-Louis
Yoshida, Masaru
Kutsumi, Hiromu
Acha-Orbea, Hans
Neulinger-Muñoz, Matthias
Vey, Johannes
Eckert, Christoph
Strobel, Oliver
Hoheisel, Jörg D.
Felix, Klaus
Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
title Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
title_full Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
title_fullStr Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
title_full_unstemmed Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
title_short Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
title_sort novel autoantibody signatures in sera of patients with pancreatic cancer, chronic pancreatitis and autoimmune pancreatitis: a protein microarray profiling approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177860/
https://www.ncbi.nlm.nih.gov/pubmed/32244327
http://dx.doi.org/10.3390/ijms21072403
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