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...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
31 March 2020
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| In: |
International journal of molecular sciences
Year: 2020, Volume: 21, Issue: 7 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21072403 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms21072403 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/21/7/2403 
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| Author Notes: | Sahar Ghassem-Zadeh, Katrin Hufnagel, Andrea Bauer, Jean-Louis Frossard, Masaru Yoshida, Hiromu Kutsumi, Hans Acha-Orbea, Matthias Neulinger-Muñoz, Johannes Vey, Christoph Eckert, Oliver Strobel, Jörg D. Hoheisel and Klaus Felix |
| Summary: | 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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| Item Description: | Gesehen am 16.09.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21072403 |