Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis
Type 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glyco...
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2021-10-01
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author | Michael X. Chen Ho-Hsuan Su Ching-Ya Shiao Yu-Ting Chang Ming-Chu Chang Chih-Chin Kao San-Yuan Wang Hsi-Chang Shih I-Lin Tsai |
author_facet | Michael X. Chen Ho-Hsuan Su Ching-Ya Shiao Yu-Ting Chang Ming-Chu Chang Chih-Chin Kao San-Yuan Wang Hsi-Chang Shih I-Lin Tsai |
author_sort | Michael X. Chen |
collection | DOAJ |
description | Type 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glycopeptides from populations in Asia were found to be isobaric ions when using LC-MS/MS as an analytical tool. In this study, an analytical workflow that coupled affinity purification and stable isotope dilution LC-MS/MS was developed to dissect IgG4 glycosylation profiles for autoimmune pancreatitis. Comparing the IgG4 and glycosylation profiles among healthy controls, patients with pancreatic ductal adenocarcinoma (PDAC), and AIP, the IgG4 glycosylations from the AIP group were found to have more digalactosylation (compared to PDAC) and less monogalactosylation (compared to HC). In addition, higher fucosylation and sialylation profiles were also discovered for the AIP group. The workflow is efficient and selective for IgG4 glycopeptides, and can be used for clinical biosignature discovery. |
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issn | 1661-6596 1422-0067 |
language | English |
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publishDate | 2021-10-01 |
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spelling | doaj.art-3187c85526884c67925b6259ef5b0d602023-11-22T20:53:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211152710.3390/ijms222111527Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune PancreatitisMichael X. Chen0Ho-Hsuan Su1Ching-Ya Shiao2Yu-Ting Chang3Ming-Chu Chang4Chih-Chin Kao5San-Yuan Wang6Hsi-Chang Shih7I-Lin Tsai8Department of Pathology and Laboratory Medicine, The University of British Columbia, Victoria, BC V8Z6R5, CanadaDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 100, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 100, TaiwanDivision of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, TaiwanSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanGenomics Research Center, Academia Sinica, Taipei 115, TaiwanDepartment of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanType 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glycopeptides from populations in Asia were found to be isobaric ions when using LC-MS/MS as an analytical tool. In this study, an analytical workflow that coupled affinity purification and stable isotope dilution LC-MS/MS was developed to dissect IgG4 glycosylation profiles for autoimmune pancreatitis. Comparing the IgG4 and glycosylation profiles among healthy controls, patients with pancreatic ductal adenocarcinoma (PDAC), and AIP, the IgG4 glycosylations from the AIP group were found to have more digalactosylation (compared to PDAC) and less monogalactosylation (compared to HC). In addition, higher fucosylation and sialylation profiles were also discovered for the AIP group. The workflow is efficient and selective for IgG4 glycopeptides, and can be used for clinical biosignature discovery.https://www.mdpi.com/1422-0067/22/21/11527type 1 autoimmune pancreatitisIgG4N-glycosylationmass spectrometry |
spellingShingle | Michael X. Chen Ho-Hsuan Su Ching-Ya Shiao Yu-Ting Chang Ming-Chu Chang Chih-Chin Kao San-Yuan Wang Hsi-Chang Shih I-Lin Tsai Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis International Journal of Molecular Sciences type 1 autoimmune pancreatitis IgG4 N-glycosylation mass spectrometry |
title | Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis |
title_full | Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis |
title_fullStr | Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis |
title_full_unstemmed | Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis |
title_short | Affinity Purification Coupled to Stable Isotope Dilution LC-MS/MS Analysis to Discover IgG4 Glycosylation Profiles for Autoimmune Pancreatitis |
title_sort | affinity purification coupled to stable isotope dilution lc ms ms analysis to discover igg4 glycosylation profiles for autoimmune pancreatitis |
topic | type 1 autoimmune pancreatitis IgG4 N-glycosylation mass spectrometry |
url | https://www.mdpi.com/1422-0067/22/21/11527 |
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