title: Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus.
abstract: The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.
authors.affiliation: Resolve Therapeutics, LLC, Seattle, WA 98103;
authors.forename: John R
authors.identifier: 0000-0001-9551-0019
authors.initials: JR
authors.lastname: Doedens
authors.affiliation: EA Genomics/Q Solutions, Durham, NC 27703;
authors.forename: Wendell D
authors.identifier: 0000-0002-9676-5387
authors.initials: WD
authors.lastname: Jones
authors.affiliation: PlasmaLab International, Everett, WA 98201;
authors.forename: Kay
authors.initials: K
authors.lastname: Hill
authors.affiliation: Sage Bionetworks, Seattle, WA 98109;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mason
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101;
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Gersuk
authors.affiliation: Swedish Medical Center and University of Washington, Seattle, WA 98122;
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.affiliation: University of California, San Francisco, San Francisco, CA 94143;
authors.forename: Maria
authors.initials: M
authors.lastname: Dall'Era
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY 11030;
authors.forename: Cynthia
authors.identifier: 0000-0001-9299-0053
authors.initials: C
authors.lastname: Aranow
authors.affiliation: College of Human Medicine, Michigan State University, East Lansing, MI 48824;
authors.forename: Richard W
authors.initials: RW
authors.lastname: Martin
authors.affiliation: Metroplex Clinical Research Center, Dallas, TX 75231;
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Cohen
authors.affiliation: Metroplex Clinical Research Center, Dallas, TX 75231;
authors.forename: Roy M
authors.initials: RM
authors.lastname: Fleischmann
authors.affiliation: Altoona Center for Clinical Research, Duncansville, PA 16635;
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kivitz
authors.affiliation: Resolve Therapeutics, LLC, Seattle, WA 98103;
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Burge
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101; Sidra Medical and Research Center, Doha, Qatar; and.
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.affiliation: Department of Rheumatology, University of Washington, Seattle, WA 98109.
authors.forename: Keith B
authors.initials: KB
authors.lastname: Elkon
authors.affiliation: Resolve Therapeutics, LLC, Seattle, WA 98103; jp@resolvebio.com.
authors.forename: James A
authors.initials: JA
authors.lastname: Posada
mesh_terms: D000328:Adult; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000097:blood* / Q000276:immunology; D020733:RNA, Small Cytoplasmic / Q000097:blood; D012342:RNA, Small Nuclear / Q000097:blood
chemical_list: D001323:Autoantibodies; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear; C405483:U1 small nuclear RNA; D012313:RNA; D007372:Interferons