Observational studyFrontiers in immunology2021
IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption.
Observational study in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Proteome-wide profiling reveals dysregulated molecular features and accelerated aging in osteoporosis: A 9.8-year prospective study.Aging cell · 2024Pooled it
- Extreme PTH-Independent Hypercalcemia Mediated by a Rare Non-Osteoclastic Osteolysis Mechanism in Newly Diagnosed High-Risk Biclonal IgA Multiple Myeloma: Temporal Association with the Second Dose of Moderna mRNA-1273 COVID-19 Vaccine.International journal of molecular sciences · 2026Article
- Rheumatoid factor and anti-citrullinated protein IgA antibodies in the diagnosis, prognosis and monitoring of patients with rheumatoid arthritis.Journal of translational autoimmunity · 2025Review
- Review
- Neutrophils: a Central Point of Interaction Between Immune Cells and Nonimmune Cells in Rheumatoid Arthritis.Clinical reviews in allergy & immunology · 2025Review
- Biomarker understanding first lessons from drug development for IgA-driven autoimmune and fibrotic diseases.Cambridge prisms. Precision medicine · 2025Review
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head.Annals of medicine · 2024Review
- Exploring the Link between Hydrodynamic Size and Immunoglobulins of Circulating Immune Complexes in Rheumatoid Arthritis Patients.International journal of molecular sciences · 2024Article
- Autoantibodies Serum Level and 10-Year Risk of Fractures Evaluated by FRAXOpen access rheumatology : research and reviews · 2024Article
- Antagonizing FcαR1 (CD89) as treatment in IgA-mediated chronic inflammation and autoimmunity.Frontiers in immunology · 2023Article
- Fcα Receptor-1-Activated Monocytes Promote B Lymphocyte Migration and IgA Isotype Switching.International journal of molecular sciences · 2022Article
- From risk to chronicity: evolution of autoreactive B cell and antibody responses in rheumatoid arthritis.Nature reviews. Rheumatology · 2022Review
- The current status of anti-citrullinated protein antibodies and citrullinated protein-reactive B cells in the pathogenesis of rheumatoid arthritis.Molecular biology reports · 2022Review
- Anti-FcαRI Monoclonal Antibodies Resolve IgA Autoantibody-Mediated Disease.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
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