title: DNA-reactive B cells in lupus.
abstract: IgG anti-DNA antibodies are both diagnostic and pathogenic for systemic lupus erythematosus (SLE). They contribute to tissue inflammation through direct tissue binding and to systemic inflammation through activation of Toll-like receptors by nucleic acid-containing immune complexes. IgG DNA-reactive antibodies originate when B cell tolerance mechanisms are impaired. The heterogeneous immune perturbations in SLE lead to the survival and activation of DNA-reactive B cells in various B cell subsets at distinct stages of B cell maturation and differentiation. We propose that the spectrum of B cell alterations and failed tolerance mechanisms for DNA-reactive B cells in lupus patients is best understood by studying genetic risk alleles. This implies that the B cells producing IgG anti-DNA antibodies and the failed tolerance mechanisms(s) will differ across patients. A better understanding of these differences should lead to better patient stratification, improved outcomes of clinical trials, and the identification of novel therapeutic targets.
authors: Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, North Shore-LIJ, 350 Community Drive, Manhasset, NY 11030, USA.
authors: Jolien
authors: J
authors: Suurmond
authors: Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, North Shore-LIJ, 350 Community Drive, Manhasset, NY 11030, USA; PhD Program in Molecular Medicine, Hofstra-Northwell School of Medicine, 500 Hofstra Blvd, Hempstead, NY 11549, USA.
authors: Justine
authors: J
authors: Calise
authors: Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, North Shore-LIJ, 350 Community Drive, Manhasset, NY 11030, USA.
authors: Susan
authors: S
authors: Malkiel
authors: Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, North Shore-LIJ, 350 Community Drive, Manhasset, NY 11030, USA. Electronic address: bdiamond@northwell.edu.
authors: Betty
authors: B
authors: Diamond
mesh_terms: D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D012306:Risk
chemical_list: D000974:Antibodies, Antinuclear; D004247:DNA