title: Systematic identification of novel SLE related autoantibodies responsible for type I IFN production in human plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells [pDC], also known as type I interferon [IFN] producing cells, play a significant role in the pathogenesis of systemic lupus erythematosus [SLE]. The current study was undertaken to identify novel SLE autoantibody specificities associated with interferon-inducing activity in human pDCs. We found that immune complex mixtures from some Interferon signature negative [IFN-] and all interferon signature positive [IFN+] SLE patients could trigger type I IFN production by pDCs. IgGs from IFN- and IFN+ SLE patients were subsequently screened via a high throughput protein microarray to identify novel auto-antibody specifities that mediate type I IFN production by pDCs. This approach identified five novel autoantibodies that may contribute to type I IFN production by pDCs via a nucleic acid dependent mechanism. The newly identified autoantibody specificities function in a myriad of cell processess and, to date, have not been implicated in SLE pathogenesis.
authors: Janssen Pharmaceutical Research & Development, L.L.C., Innate Immunity, Spring House, PA 19477, United States. Electronic address: sadik.kassim@nih.gov.
authors: Sadik H
authors: SH
authors: Kassim
authors: Jarrat
authors: J
authors: Jordan
authors: Jessica
authors: J
authors: Schreiter
authors: Sreedevi
authors: S
authors: Adhikarakunnathu
authors: Fred
authors: F
authors: Baribaud
authors: Lani
authors: L
authors: San Mateo
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D040081:Protein Array Analysis
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016898:Interferon-alpha
keywords: Autoimmune; Innate immunity; Plasmacytoid dendritic cells; Protein array; SLE; Type I interferons