ArticleArthritis research & therapy2016
In vitro eradication of citrullinated protein specific B-lymphocytes of rheumatoid arthritis patients by targeted bifunctional nanoparticles.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- Immunomodulatory Nanomaterials: Design Strategies, Mechanisms, Biomedical Applications, and Future Perspectives.Biomedicines · 2026Review
- Review
- Effect of Antigen Valency on Autoreactive B-Cell Targeting.Molecular pharmaceutics · 2024Article
- Role of ceRNA network in inflammatory cells of rheumatoid arthritis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- The interaction between nanoparticles and immune system: application in the treatment of inflammatory diseases.Journal of nanobiotechnology · 2022Review
- Nanoparticle-Based Drug Delivery Systems for Induction of Tolerance and Treatment of Autoimmune Diseases.Frontiers in bioengineering and biotechnology · 2022Review
- Biologia Futura: Emerging antigen-specific therapies for autoimmune diseases.Biologia futura · 2021Review
- Exploiting CD22 To Selectively Tolerize Autoantibody Producing B-Cells in Rheumatoid Arthritis.ACS chemical biology · 2019Article
- Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide-Specific Antibodies in Rheumatoid Arthritis.International journal of molecular sciences · 2018Article
- Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis.Clinical rheumatology · 2017Article
- Antigen-specific immunotherapies in rheumatic diseases.Nature reviews. Rheumatology · 2017Review
- Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment.Journal of ophthalmology · 2017Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutoreactive B cells are crucial players in the pathogenesis of rheumatoid arthritis (RA). Autoantibodies specific for citrullinated proteins (ACPA), present in the serum of approximately 60-70 % of patients, have a pathogenic role in the disease. B cell depleting therapies may result in a transient immunosuppression, increasing the risk of infections. Our aim was to develop a new therapeutic approach to selectively deplete the ACPA producing autoreactive B cells.
methodsTo target B cells synthetic citrullinated peptide derived from the β chain of fibrin, β60-74Cit 60,72,74 (β60-74Cit), the predominant epitope recognized by ACPA was used. Complement dependent cytotoxicity (CDC) was induced by a modified peptide derived from gp120 of HIV-1. To trigger CDC both the targeting peptide and the complement activating peptide were covalently coupled in multiple copies to the surface of poly (DL-lactic-co-glycolic acid) nanoparticles (NPs). Ex vivo antibody synthesis was examined by ELISA and ELISpot. CDC was tested after dead cell staining by flow cytometry.
resultsThe β60-74Cit peptide was selectively recognized by a small subset of B cells from RA patients having high level of peptide specific serum antibody, suggesting that the peptide can target diseased B cells. The modified gp120 peptide covalently coupled to NPs induced the formation of the complement membrane attack complex, C5b-9 in human serum. We show here for the first time that bifunctional NPs coupled to multiple copies of both the targeting peptide and the complement activating effector peptide on their surface significantly reduce β60-74Cit peptide specific ex vivo ACPA production, by inducing complement dependent lysis of the citrullinated peptide specific B cells of seropositive RA patients.
conclusionsBifunctional NPs covalently coupled to autoantigen epitope peptide and to a lytic peptide activating complement may specifically target and deplete the peptide specific autoreactive B-cells.
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