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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7177860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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