title: Association of anti-nucleoprotein autoantibodies with upregulation of Type I interferon-inducible gene transcripts and dendritic cell maturation in systemic lupus erythematosus.
abstract: Lupus patients selectively produce autoantibodies against nucleoproteins. Since the RNA/DNA components of these autoantigens are endogenous TLR ligands capable of stimulating Type I interferon (IFN-I) production, we asked whether autoantibodies against the ribonucleoproteins Sm/RNP and Ro60 and double-stranded DNA are associated with high levels of IFN-I. IFN-I levels were increased in SLE (n = 88) vs. other autoimmune diseases (n = 82) and controls (n = 57) (P < 0.0001) and were associated positively with autoantibodies against Sm/RNP, Ro60/La, and dsDNA but negatively with anti-phospholipid. Low numbers of circulating plasmacytoid and myeloid dendritic cells also were associated with these autoantibodies. The IFN-I and dendritic cell abnormalities correlated with disease severity and were not therapy-related. These findings suggest that immunostimulatory nucleic acid components of autoantigens may act as endogenous adjuvants by promoting IFN-I production and dendritic cell maturation, helping to explain the high prevalence of autoantibodies against nucleoprotein antigens in SLE.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Haoyang
authors.initials: H
authors.lastname: Zhuang
authors.forename: Sonali
authors.initials: S
authors.lastname: Narain
authors.forename: Eric
authors.initials: E
authors.lastname: Sobel
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Hanno B
authors.initials: HB
authors.lastname: Richards
authors.forename: Mark
authors.initials: M
authors.lastname: Segal
authors.forename: Carol
authors.initials: C
authors.lastname: Stewart
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D016898:Interferon-alpha / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008297:Male; D064547:Myxovirus Resistance Proteins; D020733:RNA, Small Cytoplasmic / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology*; D012720:Severity of Illness Index; D015854:Up-Regulation; D000099207:SS-A Antigen
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004247:DNA; D019204:GTP-Binding Proteins; D007370:Interferon Type I; D016898:Interferon-alpha; D064547:Myxovirus Resistance Proteins; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; C116006:RO60 protein, human; D000099207:SS-A Antigen