ArticleJournal of autoimmunity2012
The constant region contributes to the antigenic specificity and renal pathogenicity of murine anti-DNA antibodies.
Article in Journal of autoimmunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 50 citations in OpenAlex.
- Tau pSer396 and pSer404 Define Distinct Epitope Regions Linked to Different Antibody Functions.bioRxiv : the preprint server for biology · 2026Article
- New insights into antibody structure with implications for specificity, variable region restriction and isotype choice.Nature reviews. Immunology · 2025Review
- Tau-targeting therapies for Alzheimer disease: current status and future directions.Nature reviews. Neurology · 2023Review
- The Binding Mechanisms of Antibodies to DNA from Healthy Subjects and Patients with Systemic Lupus Erythematosus: The Role of Monogamous Bivalency and Fc Dependence.ImmunoHorizons · 2021Article
- Recombinant Proteins and Monoclonal Antibodies.Advances in biochemical engineering/biotechnology · 2021Review
- Antigen-binding affinity and thermostability of chimeric mouse-chicken IgY and mouse-human IgG antibodies with identical variable domains.Scientific reports · 2019Article
- ALW peptide ameliorates lupus nephritis in MRL/lpr mice.Arthritis research & therapy · 2019Article
- Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies.Frontiers in immunology · 2019Review
- Article
- Fn14 Deficiency Ameliorates Anti-dsDNA IgG-Induced Glomerular Damage in SCID Mice.Journal of immunology research · 2018Article
- CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus.Clinical immunology (Orlando, Fla.) · 2017Article
- Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus.Frontiers in immunology · 2017Review
- Estrogen receptor alpha promotes lupus in (NZB×NZW)F1 mice in a B cell intrinsic manner.Clinical immunology (Orlando, Fla.) · 2017Article
- Anti-Double-Stranded DNA IgG Participates in Renal Fibrosis through Suppressing the Suppressor of Cytokine Signaling 1 Signals.Frontiers in immunology · 2017Article
- Accelerated Systemic Autoimmunity in the Absence of Somatic Hypermutation in 564Igi: A Mouse Model of Systemic Lupus with Knocked-In Heavy and Light Chain Genes.Frontiers in immunology · 2017Article
- Scarcity of autoreactive human blood IgAEuropean journal of immunology · 2016Article
- The role of B cells and autoantibodies in neuropsychiatric lupus.Autoimmunity reviews · 2016Review
- Update on Biologic Therapies for Systemic Lupus Erythematosus.Current rheumatology reports · 2016Review
- A peptide mimic blocks the cross-reaction of anti-DNA antibodies with glomerular antigens.Clinical and experimental immunology · 2016Article
- Ig Constant Region Effects on Variable Region Structure and Function.Frontiers in microbiology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Affinity for DNA and cross-reactivity with renal antigens are associated with enhanced renal pathogenicity of lupus autoantibodies. In addition, certain IgG subclasses are enriched in nephritic kidneys, suggesting that isotype may determine the outcome of antibody binding to renal antigens. To investigate if the isotype of DNA antibodies affects renal pathogenicity by influencing antigen binding, we derived IgM, IgG1, IgG2b and IgG2a forms of the PL9-11 antibody (IgG3 anti-DNA) by in vitro class switching or PCR cloning. The affinity and specificity of PL9-11 antibodies for nuclear and renal antigens were analyzed using ELISA, Western blotting, surface plasmon resonance (SPR), binding to mesangial cells, and glomerular proteome arrays. Renal deposition and pathogenicity were assayed in mice injected with PL9-11 hybridomas. We found that PL9-11 and its isotype-switched variants had differential binding to DNA and chromatin (IgG3>IgG2a>IgG1>IgG2b>IgM) by direct and competition ELISA, and SPR. In contrast, in binding to laminin and collagen IV the IgG2a isotype actually had the highest affinity. Differences in affinity of PL9-11 antibodies for renal antigens were mirrored in analysis of specificity for glomeruli, and were associated with significant differences in renal pathogenicity in vivo and survival. Our novel findings indicate that the constant region plays an important role in the nephritogenicity of antibodies to DNA by affecting immunoglobulin affinity and specificity. Increased binding to multiple glomerular and/or nuclear antigens may contribute to the renal pathogenicity of anti-DNA antibodies of the IgG2a and IgG3 isotype. Finally, class switch recombination may be another mechanism by which B cell autoreactivity is generated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.