Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
| Autor: | Katrin Hufnagel, Oliver Strobel, Jörg D. Hoheisel, Christoph Eckert, Andrea S. Bauer, Hiromu Kutsumi, Jean Louis Frossard, Hans Acha-Orbea, Masaru Yoshida, Sahar Ghassem-Zadeh, Klaus Felix, Johannes Vey, Matthias Neulinger-Muñoz |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine pancreatic cancer lcsh:Chemistry 0302 clinical medicine antibodies lcsh:QH301-705.5 Spectroscopy Aged 80 and over biology General Medicine Middle Aged Computer Science Applications 030220 oncology & carcinogenesis Protein microarray Female Antibody autoimmune pancreatitis type 1 and type 2 Adult Patients Autoimmune Pancreatitis Protein Array Analysis microarray protein Article Catalysis Autoimmune Diseases Diagnosis Differential Inorganic Chemistry chronic pancreatitis 03 medical and health sciences Antigen Pancreatitis Chronic Pancreatic cancer medicine Humans Clinical significance Physical and Theoretical Chemistry Molecular Biology Aged Autoantibodies Autoimmune pancreatitis business.industry Organic Chemistry Autoantibody medicine.disease Pancreatic Neoplasms 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Immunoglobulin G Immunology biology.protein Pancreatitis business |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 7 International Journal of Molecular Sciences, Vol 21, Iss 2403, p 2403 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21072403 |
| Popis: | 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&rsquo 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. |
| Databáze: | OpenAIRE |
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