ArticleThe Journal of experimental medicine2004
Pathogenic profiles and molecular signatures of antinuclear autoantibodies rescued from NZM2410 lupus mice.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 69 citations in OpenAlex.
- Loss of an IgG plasma cell checkpoint in patients with lupus.The Journal of allergy and clinical immunology · 2019Article
- The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis.Clinical immunology (Orlando, Fla.) · 2017Review
- Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis.Inflammation · 2016Article
- What is damaging the kidney in lupus nephritis?Nature reviews. Rheumatology · 2016Review
- Monoclonal antibodies specific for human IgM Fc receptor inhibit ligand-binding activity.Monoclonal antibodies in immunodiagnosis and immunotherapy · 2014Article
- Discovery of biomarkers for systemic lupus erythematosus using a library of synthetic autoantigen surrogates.Journal of immunological methods · 2014Article
- Splenic B-1a Cells Expressing CD138 Spontaneously Secrete Large Amounts of Immunoglobulin in Naïve Mice.Frontiers in immunology · 2014Article
- Lupus-prone strains vary in susceptibility to antibody-mediated end organ disease.Genes and immunity · 2013Article
- IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn-/- mice.European journal of immunology · 2013Article
- Activation-induced deaminase contributes to the antibody-independent role of B cells in the development of autoimmunity.Autoimmunity · 2012Article
- Murine lupus strains differentially model unique facets of human lupus serology.Clinical and experimental immunology · 2012Article
- Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- L2pB1: a new player in autoimmunity.Molecular immunology · 2011Review
- Activation-induced deaminase-deficient MRL/lpr mice secrete high levels of protective antibodies against lupus nephritis.Arthritis and rheumatism · 2011Article
- Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models.Arthritis research & therapy · 2011Review
- Anti-nuclear antibody reactivity in lupus may be partly hard-wired into the primary B-cell repertoire.Molecular immunology · 2009Article
- Molecular hallmarks of anti-chromatin antibodies associated with the lupus susceptibility locus, Sle1.Molecular immunology · 2009Article
- CXCR4/CXCL12 hyperexpression plays a pivotal role in the pathogenesis of lupus.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.The Journal of clinical investigation · 2009Article
- Pathogenic anti-DNA antibodies modulate gene expression in mesangial cells: involvement of HMGB1 in anti-DNA antibody-induced renal injury.Immunology letters · 2008Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges. Although nephrophilic immunoglobulin (Ig) M and IgG antibodies were the most pathogenic, the dsDNA-binding antibodies were modestly so; in contrast, antinucleosome antibodies were clearly not pathogenic. Compared with the nonnuclear antigen-binding monoclonal antibodies rescued from the same mice, ANAs exhibited increased utilization of VH5/7183 genes and highly cationic heavy chain (HC) CDR3 regions. Most intriguingly, the CDR3 regions of the ANAs exhibited alternating arginine/lysine peaks at H96, H98, and H100, with neutral troughs at H95, H97, and H99. To summarize, glomerular-binding anti-dsDNA antibodies appear to be the most pathogenic variety of lupus autoantibodies. The presence of an alternating charge pattern in their HC CDR3 regions appears to be a prominent hallmark of ANAs.
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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.