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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/21/11527
_version_ 1797512483370434560
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.
first_indexed 2024-03-10T06:01:27Z
format Article
id doaj.art-3187c85526884c67925b6259ef5b0d60
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T06:01:27Z
publishDate 2021-10-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
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
work_keys_str_mv AT michaelxchen affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT hohsuansu affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT chingyashiao affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT yutingchang affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT mingchuchang affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT chihchinkao affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT sanyuanwang affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT hsichangshih affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis
AT ilintsai affinitypurificationcoupledtostableisotopedilutionlcmsmsanalysistodiscoverigg4glycosylationprofilesforautoimmunepancreatitis