Association of anti-nucleoprotein autoantibodies with upregulation of Type I interferon-inducible gene transcripts and dendritic cell maturation in systemic lupus erythematosus.
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.
Zhuang
Haoyang
H
Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, FL 32610, USA.
Narain
Sonali
S
Sobel
Eric
E
Lee
Pui Y
PY
Nacionales
Dina C
DC
Kelly
Kindra M
KM
Richards
Hanno B
HB
Segal
Mark
M
Stewart
Carol
C
Satoh
Minoru
M
Reeves
Westley H
WH
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
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