title: Anti-DNA antibodies cross-react with C1q.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disorder that involves multiple organ systems and typically presents as a chronic inflammatory disease. Antibodies to double-stranded (ds) DNA are present in approximately 70% of patients and form nucleic acid containing immune complexes which activate dendritic cells through engagement of toll-like receptors, leading to a pro-inflammatory, pro-immunogenic milieu. In addition, anti-dsDNA antibodies deposit in kidneys to initiate glomerulonephritis. Antibodies to C1q have also been implicated in lupus nephritis and are found in 30-50% of patients. C1q is a known suppressor of immune activation and C1q deficiency is the strongest risk factor for SLE. We previously identified a subset of anti-DNA antibodies that binds the N-methyl-D-aspartate receptor. We now show that both mouse and human anti-DNA antibodies with this specificity bind C1q. These antibodies bind to Clq in glomeruli and exhibit decreased glomerular deposition in the absence of C1q. We propose that this subset of anti-DNA antibodies participates in lupus pathogenesis through direct targeting of C1q on glomeruli and also through removal of soluble C1q thereby limiting the ability of C1q to mediate immune homeostasis.
authors.affiliation: The Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Franchin
authors.forename: Myoungsun
authors.initials: M
authors.lastname: Son
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ilan
authors.initials: I
authors.lastname: Ben-Zvi
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015922:Complement C1q / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D015922:Complement C1q; D004247:DNA
keywords: Anti-DNA antibody; Complement C1q; Lupus