Galectin-3 and prohibitin 1 are autoantigens in IgG4-related cholangitis without clear-cut protective effects against toxic bile acids.
IgG4-related systemic disease
biliary bicarbonate umbrella
cholangiopathy
cholestasis
immune-mediated disease
secretory organs
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
30
06
2023
accepted:
15
12
2023
medline:
9
2
2024
pubmed:
9
2
2024
entrez:
9
2
2024
Statut:
epublish
Résumé
IgG4-related cholangitis (IRC) is the hepatobiliary manifestation of IgG4-related disease, a systemic B cell-driven fibro-inflammatory disorder. Four autoantigens have recently been described in IgG4-RD: annexin A11, galectin-3, laminin 511-E8, and prohibitin 1. We have previously reported a protective role of annexin A11 and laminin 511-E8 in human cholangiocytes against toxic bile acids. Here, we explored the potentially protective role of the carbohydrate-binding lectin galectin-3 and the scaffold proteins prohibitins 1 and 2. Anti-galectin-3, anti-prohibitin 1 and 2 autoantibody positivity in IRC and healthy and disease (primary sclerosing cholangitis (PSC)) control sera was assessed by ELISA/liquid chromatography-tandem mass spectrometry (LC-MS/MS). Human H69 cholangiocytes were subjected to short hairpin RNA (shRNA) knockdown targeting galectin-3 ( Anti-galectin-3 autoantibodies were detected in 13.5% of individuals with IRC but not in PSC. Knockdown of A subset of individuals with IRC have autoantibodies against galectin-3 and prohibitin 1. Gene-specific knockdown, pharmacological inhibition, and recombinant protein substitution did not clearly disclose a protective role of these autoantigens in human cholangiocytes against toxic bile acids. The involvement of these autoantibodies in processes surpassing epithelial secretion remains to be elucidated.
Sections du résumé
Background and aims
IgG4-related cholangitis (IRC) is the hepatobiliary manifestation of IgG4-related disease, a systemic B cell-driven fibro-inflammatory disorder. Four autoantigens have recently been described in IgG4-RD: annexin A11, galectin-3, laminin 511-E8, and prohibitin 1. We have previously reported a protective role of annexin A11 and laminin 511-E8 in human cholangiocytes against toxic bile acids. Here, we explored the potentially protective role of the carbohydrate-binding lectin galectin-3 and the scaffold proteins prohibitins 1 and 2.
Methods
Anti-galectin-3, anti-prohibitin 1 and 2 autoantibody positivity in IRC and healthy and disease (primary sclerosing cholangitis (PSC)) control sera was assessed by ELISA/liquid chromatography-tandem mass spectrometry (LC-MS/MS). Human H69 cholangiocytes were subjected to short hairpin RNA (shRNA) knockdown targeting galectin-3 (
Results
Anti-galectin-3 autoantibodies were detected in 13.5% of individuals with IRC but not in PSC. Knockdown of
Conclusions
A subset of individuals with IRC have autoantibodies against galectin-3 and prohibitin 1. Gene-specific knockdown, pharmacological inhibition, and recombinant protein substitution did not clearly disclose a protective role of these autoantigens in human cholangiocytes against toxic bile acids. The involvement of these autoantibodies in processes surpassing epithelial secretion remains to be elucidated.
Identifiants
pubmed: 38332916
doi: 10.3389/fimmu.2023.1251134
pmc: PMC10851949
doi:
Substances chimiques
Annexins
0
Autoantibodies
0
Autoantigens
0
Bile Acids and Salts
0
Galectin 3
0
Immunoglobulin G
0
Prohibitins
0
PHB protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1251134Informations de copyright
Copyright © 2024 Kersten, Trampert, Hubers, Tolenaars, Vos, van de Graaf and Beuers.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Curr Biol. 2006 Feb 21;16(4):408-14
pubmed: 16488876
J Hepatol. 2022 Sep;77(3):761-806
pubmed: 35738507
J Invest Dermatol. 2012 Dec;132(12):2828-37
pubmed: 22785133
Apoptosis. 2005 Mar;10(2):267-75
pubmed: 15843888
Nat Rev Gastroenterol Hepatol. 2022 Mar;19(3):185-197
pubmed: 34750548
Front Immunol. 2017 Mar 13;8:235
pubmed: 28348556
Nat Rev Immunol. 2023 Nov;23(11):763-778
pubmed: 37095254
Hepatology. 2010 Dec;52(6):2096-108
pubmed: 20890892
Ann N Y Acad Sci. 2018 Feb;1413(1):92-103
pubmed: 29377160
J Immunol. 2006 Jan 15;176(2):778-89
pubmed: 16393961
Glycobiology. 2013 Jul;23(7):893-903
pubmed: 23550149
J Immunol. 2013 Jan 15;190(2):723-36
pubmed: 23241883
Gut. 2016 Aug;65(8):1322-32
pubmed: 26964842
Hepatology. 2013 Jun;57(6):2390-8
pubmed: 23300096
Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14496-501
pubmed: 19706535
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20783-8
pubmed: 24297891
Hepatology. 2015 Oct;62(4):1237-48
pubmed: 26109312
EMBO J. 2018 Aug 15;37(16):
pubmed: 30049713
Gut. 2018 Apr;67(4):728-735
pubmed: 28765476
J Allergy Clin Immunol. 2014 Sep;134(3):679-87
pubmed: 24815737
Am J Physiol. 1994 Jun;266(6 Pt 1):G1060-70
pubmed: 8023938
Chem Biol. 2013 Mar 21;20(3):316-31
pubmed: 23521790
J Allergy Clin Immunol. 2019 Feb;143(2):736-745.e6
pubmed: 29852256
Int J Biochem Cell Biol. 2021 Jan;130:105881
pubmed: 33181315
Traffic. 2007 Apr;8(4):379-88
pubmed: 17319896
J Biol Chem. 2008 Feb 22;283(8):4699-713
pubmed: 18086671
Gastroenterology. 2008 Mar;134(3):706-15
pubmed: 18222442
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17079-86
pubmed: 17079490
J Biol Chem. 2000 Sep 22;275(38):29579-86
pubmed: 10862763
Sci Transl Med. 2018 Aug 8;10(453):
pubmed: 30089633
Int J Cancer. 2015 Oct 15;137(8):1791-9
pubmed: 24895251
J Immunol. 2004 Jan 1;172(1):493-502
pubmed: 14688359
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1401-1409
pubmed: 28782655
Traffic. 2013 Sep;14(9):1014-27
pubmed: 23710780
J Pharmacol Exp Ther. 2014 Nov;351(2):336-43
pubmed: 25194021
Biochimie. 2002 Dec;84(12):1207-20
pubmed: 12628297
JHEP Rep. 2021 Oct 09;3(6):100385
pubmed: 34816110
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5060-5
pubmed: 16549783
Hepatology. 2010 Oct;52(4):1489-96
pubmed: 20721884
Apoptosis. 2015 Sep;20(9):1135-49
pubmed: 26091791
Am J Gastroenterol. 2016 May;111(5):733-43
pubmed: 27091321
J Ind Microbiol Biotechnol. 2013 Apr;40(3-4):257-74
pubmed: 23385853
J Hepatol. 2022 Feb;76(2):319-331
pubmed: 34718050
Ann Rheum Dis. 2015 Jan;74(1):190-5
pubmed: 24817416
Cell Mol Life Sci. 2020 Sep;77(18):3525-3546
pubmed: 32062751
J Hepatol. 2002 Apr;36(4):459-65
pubmed: 11943415
PLoS One. 2015 May 01;10(5):e0125331
pubmed: 25932630
Hepatology. 2011 Sep 2;54(3):940-8
pubmed: 21674559
Hepatology. 2013 Sep;58(3):1084-93
pubmed: 23564624
Eur J Cell Biol. 2015 Jul-Sep;94(7-9):309-15
pubmed: 26059399
Front Immunol. 2021 Jan 29;11:605214
pubmed: 33584677
Hepatology. 2012 Jan;55(1):173-83
pubmed: 21932391
Arthritis Rheumatol. 2020 Apr;72(4):687-693
pubmed: 31612628
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
J Biol Chem. 2012 Dec 28;287(53):44684-93
pubmed: 23118221
Cancer Res. 2003 Dec 1;63(23):8302-11
pubmed: 14678989
Cell Mol Life Sci. 2002 Mar;59(3):445-55
pubmed: 11964123
Hepatology. 2014 May;59(5):1954-63
pubmed: 24375491
Am J Gastroenterol. 2018 May;113(5):765-772
pubmed: 29549357
J Neuroimmunol. 2008 Mar;195(1-2):151-6
pubmed: 18384886
J Cell Sci. 2018 Jun 11;131(11):
pubmed: 29748377
Glycobiology. 2006 Jan;16(1):36-45
pubmed: 16166603
Neurosci Lett. 2003 Mar 13;339(1):62-6
pubmed: 12618301
Hepatology. 2018 Apr;67(4):1420-1440
pubmed: 28922472
J Leukoc Biol. 2007 Aug;82(2):300-10
pubmed: 17456800
Int J Cancer. 2000 Feb 15;85(4):545-54
pubmed: 10699929
Biochim Biophys Acta. 2006 Apr;1760(4):616-35
pubmed: 16478649