IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption.
Animals
Antigen-Antibody Complex
/ immunology
Arthritis, Rheumatoid
/ blood
Autoantibodies
/ immunology
Bone Resorption
/ blood
Cattle
Extracellular Traps
/ metabolism
Humans
Immunoglobulin A
/ immunology
Interleukin-6
/ metabolism
Interleukin-8
/ metabolism
Knee Joint
/ immunology
Osteoclasts
/ immunology
Synovial Fluid
/ immunology
ACPA
IgA
autoantibodies
bone resorption
osteoclast
rheumatoid arthritis
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
01
2021
accepted:
07
06
2021
entrez:
19
7
2021
pubmed:
20
7
2021
medline:
25
9
2021
Statut:
epublish
Résumé
Autoantibodies are detected in most patients with rheumatoid arthritis (RA) and can be of the IgM, IgG or IgA subclass. Correlations between IgA autoantibodies and more severe disease activity have been previously reported, but the functional role of IgA autoantibodies in the pathogenesis of RA is ill understood. In this study, we explored the effect of IgA immune complexes on osteoclast mediated bone resorption. Anti-citrullinated peptide antibody (ACPA) and anti-carbamylated protein (anti-CarP) antibody levels of the IgA and IgG isotype and rheumatoid factor (RF) IgA were determined in synovial fluid (SF) of RA patients. Monocytes, neutrophils, and osteoclasts were stimulated with precipitated immune complexes from SF of RA patients or IgA- and IgG-coated beads. Activation was determined by neutrophil extracellular trap (NET) release, cytokine secretion, and bone resorption. NET formation by neutrophils was enhanced by SF immune complexes compared to immune complexes from healthy or RA serum. Monocytes stimulated with isolated SF immune complexes released IL-6 and IL-8, which correlated with the levels of ACPA IgA levels in SF. Osteoclasts cultured in the presence of supernatant of IgA-activated monocytes resorbed significantly more bone compared to osteoclasts that were cultured in supernatant of IgG-activated monocytes (p=0.0233). Osteoclasts expressed the Fc receptor for IgA (FcαRI; CD89) and Fc gamma receptors. IgA-activated osteoclasts however produced significantly increased levels of IL-6 (p<0.0001) and IL-8 (p=0.0007) compared to IgG-activated osteoclasts. Both IL-6 (p=0.03) and IL-8 (p=0.0054) significantly enhanced bone resorption by osteoclasts. IgA autoantibodies induce release of IL-6 and IL-8 by immune cells as well as osteoclasts, which enhances bone resorption by osteoclasts. We anticipate that this will result in more severe disease activity in RA patients. Targeting IgA-FcαRI interactions therefore represents a promising novel therapeutic strategy for RA patients with IgA autoantibodies.
Identifiants
pubmed: 34276648
doi: 10.3389/fimmu.2021.651049
pmc: PMC8281931
doi:
Substances chimiques
Antigen-Antibody Complex
0
Autoantibodies
0
CXCL8 protein, human
0
IL6 protein, human
0
Immunoglobulin A
0
Interleukin-6
0
Interleukin-8
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
651049Informations de copyright
Copyright © 2021 Breedveld, van Gool, van Delft, van der Laken, de Vries, Jansen and van Egmond.
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
J Clin Pathol. 1990 Dec;43(12):997-1003
pubmed: 2266187
Ann Rheum Dis. 2016 Apr;75(4):721-9
pubmed: 26612338
J Clin Invest. 2012 May;122(5):1791-802
pubmed: 22505457
Am J Pathol. 2001 Nov;159(5):1689-99
pubmed: 11696430
J Immunol. 2007 Dec 1;179(11):7497-505
pubmed: 18025194
J Bone Miner Metab. 2007;25(6):337-44
pubmed: 17968485
Arthritis Res Ther. 2019 Feb 4;21(1):45
pubmed: 30717793
J Bone Miner Res. 1990 Jul;5(7):781-9
pubmed: 2204254
J Immunol. 2016 Dec 15;197(12):4552-4559
pubmed: 27913645
Arthritis Rheum. 2013 Apr;65(4):899-910
pubmed: 23310951
Scand J Rheumatol. 1995;24(6):372-5
pubmed: 8610222
Lancet. 2008 Mar 22;371(9617):987-97
pubmed: 18358926
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8222-6
pubmed: 9653168
Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17372-7
pubmed: 21987802
J Exp Med. 2016 Sep 19;213(10):1937-50
pubmed: 27621417
Arthritis Res Ther. 2018 Feb 7;20(1):24
pubmed: 29415763
Ann Rheum Dis. 2004 Dec;63(12):1587-93
pubmed: 15547083
Immunol Invest. 2007;36(3):285-91
pubmed: 17558711
Agents Actions. 1994 Mar;41(1-2):90-2
pubmed: 8079829
Arthritis Rheum. 2006 Nov;54(11):3551-63
pubmed: 17075861
J Cell Physiol. 2016 Jun;231(6):1249-60
pubmed: 26491867
Cell Physiol Biochem. 2017;41(4):1360-1369
pubmed: 28278513
Cell Mol Immunol. 2021 Jun;18(6):1528-1544
pubmed: 32203195
J Res Med Sci. 2014 Sep;19(9):823-6
pubmed: 25535495
J Immunol. 2014 Mar 1;192(5):2374-83
pubmed: 24493821
Ann Rheum Dis. 2014 May;73(5):854-60
pubmed: 23520034
J Transl Med. 2017 Feb 15;15(1):36
pubmed: 28202039
J Rheumatol. 2011 Jul;38(7):1265-72
pubmed: 21459947
Sci Transl Med. 2013 Mar 27;5(178):178ra40
pubmed: 23536012
Immunity. 2017 Feb 21;46(2):183-196
pubmed: 28228278
Nat Rev Rheumatol. 2018 Dec;14(12):714-726
pubmed: 30420750
Arthritis Res Ther. 2007;9(2):R25
pubmed: 17341304
Infect Immun. 2014 Jan;82(1):364-70
pubmed: 24191297
Arthritis Res Ther. 2011 Feb 03;13(1):R13
pubmed: 21291540
Eur J Rheumatol. 2019 Jan;6(1):29-33
pubmed: 30973322
Front Immunol. 2018 Apr 24;9:876
pubmed: 29740454
Cells. 2020 Apr 03;9(4):
pubmed: 32260219
PLoS One. 2015 Oct 01;10(10):e0139564
pubmed: 26426806
Eur J Immunol. 2018 Sep;48(9):1563-1572
pubmed: 29879311
Arthritis Rheum. 2006 Sep;54(9):2817-29
pubmed: 16947782
Calcif Tissue Int. 2017 Jul;101(1):17-23
pubmed: 28246933
Ann Rheum Dis. 2011 Jun;70(6):1052-9
pubmed: 21406456
Arthritis Rheum. 2011 Jan;63(1):53-62
pubmed: 20954191
Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10729-34
pubmed: 23754379
J Immunol Res. 2019 Sep 15;2019:8672604
pubmed: 31637266
Ann Rheum Dis. 2007 Sep;66(9):1162-7
pubmed: 17485422
Ann Rheum Dis. 2015 Jan;74(1):234-41
pubmed: 24106048
Arthritis Rheum. 2000 Feb;43(2):250-8
pubmed: 10693863
Ann Rheum Dis. 2014 Apr;73(4):780-3
pubmed: 24336334
Int J Biochem Mol Biol. 2011;2(2):183-189
pubmed: 21968748
J Cell Physiol. 2004 Jul;200(1):99-106
pubmed: 15137062
J Bone Miner Metab. 2007;25(1):36-45
pubmed: 17187192
Rheumatology (Oxford). 2001 Jun;40(6):623-30
pubmed: 11426018
Ann Rheum Dis. 2015 Dec;74(12):2151-6
pubmed: 25115448
Endocrinology. 2005 Apr;146(4):1991-8
pubmed: 15618359
J Rheumatol. 1991 Sep;18(9):1282-4
pubmed: 1757925
Autoimmun Rev. 2014 Mar;13(3):225-30
pubmed: 24176675
Ann Rheum Dis. 1992 Jul;51(7):863-8
pubmed: 1632659
J Autoimmun. 2020 Jun;110:102392
pubmed: 31911013
Arthritis Res Ther. 2015 Feb 07;17:25
pubmed: 25889922
Front Immunol. 2018 May 28;9:1057
pubmed: 29892280
Arthritis Res Ther. 2017 Aug 15;19(1):190
pubmed: 28810902