IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption
ObjectiveAutoantibodies 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 o...
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| Format: | Article |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.651049/full |
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| author | Annelot C. Breedveld Annelot C. Breedveld Melissa M. J. van Gool Melissa M. J. van Gool Myrthe A. M. van Delft Myrthe A. M. van Delft Conny J. van der Laken Conny J. van der Laken Teun J. de Vries Ineke D. C. Jansen Marjolein van Egmond Marjolein van Egmond Marjolein van Egmond |
| author_facet | Annelot C. Breedveld Annelot C. Breedveld Melissa M. J. van Gool Melissa M. J. van Gool Myrthe A. M. van Delft Myrthe A. M. van Delft Conny J. van der Laken Conny J. van der Laken Teun J. de Vries Ineke D. C. Jansen Marjolein van Egmond Marjolein van Egmond Marjolein van Egmond |
| author_sort | Annelot C. Breedveld |
| collection | DOAJ |
| description | ObjectiveAutoantibodies 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.MethodsAnti-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.ResultsNET 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.ConclusionIgA 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. |
| first_indexed | 2024-12-15T00:49:46Z |
| format | Article |
| id | doaj.art-6bcb64771b8540f6927d00225c1804d3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-15T00:49:46Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-6bcb64771b8540f6927d00225c1804d32022-12-21T22:41:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.651049651049IgA Immune Complexes Induce Osteoclast-Mediated Bone ResorptionAnnelot C. Breedveld0Annelot C. Breedveld1Melissa M. J. van Gool2Melissa M. J. van Gool3Myrthe A. M. van Delft4Myrthe A. M. van Delft5Conny J. van der Laken6Conny J. van der Laken7Teun J. de Vries8Ineke D. C. Jansen9Marjolein van Egmond10Marjolein van Egmond11Marjolein van Egmond12Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsAmsterdam institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Rheumatology, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, NetherlandsDepartment of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsAmsterdam institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsObjectiveAutoantibodies 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.MethodsAnti-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.ResultsNET 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.ConclusionIgA 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.651049/fullACPAautoantibodiesbone resorptionIgAosteoclastrheumatoid arthritis |
| spellingShingle | Annelot C. Breedveld Annelot C. Breedveld Melissa M. J. van Gool Melissa M. J. van Gool Myrthe A. M. van Delft Myrthe A. M. van Delft Conny J. van der Laken Conny J. van der Laken Teun J. de Vries Ineke D. C. Jansen Marjolein van Egmond Marjolein van Egmond Marjolein van Egmond IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption Frontiers in Immunology ACPA autoantibodies bone resorption IgA osteoclast rheumatoid arthritis |
| title | IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption |
| title_full | IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption |
| title_fullStr | IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption |
| title_full_unstemmed | IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption |
| title_short | IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption |
| title_sort | iga immune complexes induce osteoclast mediated bone resorption |
| topic | ACPA autoantibodies bone resorption IgA osteoclast rheumatoid arthritis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.651049/full |
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