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1
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84873404949
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The interferon signature in autoimmune diseases
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Ronnblom L, Eloranta ML. The interferon signature in autoimmune diseases. Curr Opin Rheumatol 2013; 25:248–253.
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(2013)
Curr Opin Rheumatol
, vol.25
, pp. 248-253
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Ronnblom, L1
Eloranta, ML.2
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2
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84989859132
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Blood-borne Rna correlates with disease activity and Ifn-stimulated gene expression in systemic lupus erythematosus
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Doedens JR, Jones WD, Hill K, et al. Blood-borne Rna correlates with disease activity and Ifn-stimulated gene expression in systemic lupus erythematosus. J Immunol 2016; 197:2854–2863.
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(2016)
J Immunol
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, pp. 2854-2863
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Doedens, JR1
Jones, WD2
Hill, K3
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3
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84992560627
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Expression of long interspersed nuclear element 1 retroelements and induction of type I interferon in patients with systemic autoimmune disease
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Mavragani CP, Sagalovskiy I, Guo Q, et al. Expression of long interspersed nuclear element 1 retroelements and induction of type I interferon in patients with systemic autoimmune disease. Arthritis Rheumatol 2016; 68: 2686–2696.
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(2016)
Arthritis Rheumatol
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, pp. 2686-2696
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Mavragani, CP1
Sagalovskiy, I2
Guo, Q3
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4
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84992618510
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Prion-like aggregation of mitochondrial antiviral signaling protein in lupus patients is associated with increased levels of type I interferon
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Shao WH, Shu DH, Zhen Y, et al. Prion-like aggregation of mitochondrial antiviral signaling protein in lupus patients is associated with increased levels of type I interferon. Arthritis Rheumatol 2016; 68:2697–2707.
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(2016)
Arthritis Rheumatol
, vol.68
, pp. 2697-2707
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Shao, WH1
Shu, DH2
Zhen, Y3
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5
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84997077008
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Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response
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Lee JY, Park JK, Lee EY, et al. Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response. Arthritis Res Ther 2016; 18:264.
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(2016)
Arthritis Res Ther
, vol.18
, pp. 264
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Lee, JY1
Park, JK2
Lee, EY3
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6
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85030425661
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Are interferon-related biomarkers advantageous for monitoring disease activity in systemic lupus erythematosus? A longitudinal benchmark study
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Rose T, Grutzkau A, Klotsche J, et al. Are interferon-related biomarkers advantageous for monitoring disease activity in systemic lupus erythematosus? A longitudinal benchmark study. Rheumatology (Oxford) 2017; 56: 1618–1626.
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(2017)
Rheumatology (Oxford)
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, pp. 1618-1626
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Rose, T1
Grutzkau, A2
Klotsche, J3
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7
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85021075354
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Detection of interferon alpha protein & reveals differential levels and cellular sources in disease
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Using a single-molecule array (Simoa) digital ELISA technology with mAbs from two patients with APS1/APECED mutations, the authors were able to record attomolar concentrations of IFNa. An ultrasensitive and reliable IFNa protein assay for clinical use is much needed and this is a step towards that goal
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Rodero MP, Decalf J, Bondet V, et al. Detection of interferon alpha protein & reveals differential levels and cellular sources in disease. J Exp Med 2017; 214:1547–1555. Using a single-molecule array (Simoa) digital ELISA technology with mAbs from two patients with APS1/APECED mutations, the authors were able to record attomolar concentrations of IFNa. An ultrasensitive and reliable IFNa protein assay for clinical use is much needed and this is a step towards that goal.
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(2017)
J Exp Med
, vol.214
, pp. 1547-1555
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Rodero, MP1
Decalf, J2
Bondet, V3
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8
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85024906085
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Transances- && tral mapping and genetic load in systemic lupus erythematosus
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This is the largest genetic study in patients with SLE and the study establishes that more than 100 risk loci are associated with the disease. Several ethnic groups were investigated and both shared and ancestry-dependent loci were identified
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Langefeld CD, Ainsworth HC, Cunninghame Graham DS, et al. Transances- && tral mapping and genetic load in systemic lupus erythematosus. Nat Commun 2017; 8:16021. This is the largest genetic study in patients with SLE and the study establishes that more than 100 risk loci are associated with the disease. Several ethnic groups were investigated and both shared and ancestry-dependent loci were identified.
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(2017)
Nat Commun
, vol.8
, pp. 16021
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Langefeld, CD1
Ainsworth, HC2
Cunninghame Graham, DS3
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9
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85049948740
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Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population
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Wen L, Zhu C, Zhu Z, et al. Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population. Ann Rheum Dis 2018; 77:417.
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(2018)
Ann Rheum Dis
, vol.77
, pp. 417
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Wen, L1
Zhu, C2
Zhu, Z3
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10
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85018819254
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Genome-wide association analysis reveals genetic heterogeneity of Sjogren’s syndrome according to ancestry
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Taylor KE, Wong Q, Levine DM, et al. Genome-wide association analysis reveals genetic heterogeneity of Sjogren’s syndrome according to ancestry. Arthritis Rheumatol 2017; 69:1294–1305.
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(2017)
Arthritis Rheumatol
, vol.69
, pp. 1294-1305
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Taylor, KE1
Wong, Q2
Levine, DM3
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11
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85019738660
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Common variants near Ikzf1 are associated with primary Sjogren’s syndrome in Han Chinese
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Qu SS, Du Y, Chang SH, et al. Common variants near Ikzf1 are associated with primary Sjogren’s syndrome in Han Chinese. PLos One 2017; 12: e0177320.
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(2017)
PLos One
, vol.12
, pp. e0177320
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Qu, SS1
Du, Y2
Chang, SH3
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12
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85052555303
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The Stat4 Sle risk allele & Rs7574865[T] is associated with increased Il-12-induced IFN-g production in T cells from patients with SLE
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[Epub ahead of print] The functional consequences of the STAT4 risk gene variant in intron 3 has been unknown for 10 years. This study establishes a molecular connection between the risk gene variant and an increased IL-12 and IFNa response in T cells from patients with SLE. JAK inhibitors could block the T cell response
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Hagberg N, Joelsson M, Leonard D, et al. The Stat4 Sle risk allele & Rs7574865[T] is associated with increased Il-12-induced IFN-g production in T cells from patients with SLE. Ann Rheum Dis 2018. [Epub ahead of print] The functional consequences of the STAT4 risk gene variant in intron 3 has been unknown for 10 years. This study establishes a molecular connection between the risk gene variant and an increased IL-12 and IFNa response in T cells from patients with SLE. JAK inhibitors could block the T cell response.
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(2018)
Ann Rheum Dis
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Hagberg, N1
Joelsson, M2
Leonard, D3
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13
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85010756188
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Mirna-451a targets Ifn regulatory factor 8 for the progression of systemic lupus erythematosus
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Cheng J, Wu R, Long L, et al. Mirna-451a targets Ifn regulatory factor 8 for the progression of systemic lupus erythematosus. Inflammation 2017; 40: 676–687.
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(2017)
Inflammation
, vol.40
, pp. 676-687
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Cheng, J1
Wu, R2
Long, L3
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14
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85015368237
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Microrna-302d targets Irf9 to regulate the & Ifn-induced gene expression in Sle
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MicroRNA can control the IFN response, and in this study, the authors show that microRNA-320d is low in monocytes from patients with SLE and correlates with an IFN signature. Treatment of pristane-induced lupus with miR-320d downregulated the IFN response, but effect on clinical disease activity remains to be established
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Smith S, Fernando T, Wu PW, et al. Microrna-302d targets Irf9 to regulate the & Ifn-induced gene expression in Sle. J Autoimmun 2017; 79:105–111. MicroRNA can control the IFN response, and in this study, the authors show that microRNA-320d is low in monocytes from patients with SLE and correlates with an IFN signature. Treatment of pristane-induced lupus with miR-320d downregulated the IFN response, but effect on clinical disease activity remains to be established.
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(2017)
J Autoimmun
, vol.79
, pp. 105-111
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Smith, S1
Fernando, T2
Wu, PW3
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15
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85022326127
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Brief report: deficiency of complement 1r subcomponent in early-onset systemic lupus erythematosus: the role of disease-modifying alleles in a monogenic disease
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Demirkaya E, Zhou Q, Smith CK, et al. Brief report: deficiency of complement 1r subcomponent in early-onset systemic lupus erythematosus: the role of disease-modifying alleles in a monogenic disease. Arthritis Rheumatol 2017; 69:1832–1839.
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(2017)
Arthritis Rheumatol
, vol.69
, pp. 1832-1839
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Demirkaya, E1
Zhou, Q2
Smith, CK3
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16
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85033442355
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Lupus-associated functional polymorphism in Pnp causes cell cycle abnormalities and interferon pathway activation in human immune cells
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Ghodke-Puranik Y, Dorschner JM, Vsetecka DM, et al. Lupus-associated functional polymorphism in Pnp causes cell cycle abnormalities and interferon pathway activation in human immune cells. Arthritis Rheumatol 2017; 69:2328–2337.
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(2017)
Arthritis Rheumatol
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, pp. 2328-2337
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Ghodke-Puranik, Y1
Dorschner, JM2
Vsetecka, DM3
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17
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84921605360
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Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus
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Kariuki SN, Ghodke-Puranik Y, Dorschner JM, et al. Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. Genes Immun 2015; 16: 15–23.
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(2015)
Genes Immun
, vol.16
, pp. 15-23
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Kariuki, SN1
Ghodke-Puranik, Y2
Dorschner, JM3
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18
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85018666210
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Cd11b activation suppresses TLR- && dependent inflammation and autoimmunity in systemic lupus erythematosus
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ITGAM encodes CD11b and SLE-associated gene variants confer reduced inhibition of the type I IFN signalling pathway the present study, the authors show that activation of CD11b with a small molecule block the TLR4 activation and protects MLR/lpr mice from end organ damage. The effect on IFN production by TLR 7 and 9 activation was, however, not investigated
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Faridi MH, Khan SQ, Zhao W, et al. Cd11b activation suppresses TLR- && dependent inflammation and autoimmunity in systemic lupus erythematosus. J Clin Invest 2017; 127:1271–1283. ITGAM encodes CD11b and SLE-associated gene variants confer reduced inhibition of the type I IFN signalling pathway. In the present study, the authors show that activation of CD11b with a small molecule block the TLR4 activation and protects MLR/lpr mice from end organ damage. The effect on IFN production by TLR 7 and 9 activation was, however, not investigated.
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(2017)
J Clin Invest
, vol.127
, pp. 1271-1283
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Faridi, MH1
Khan, SQ2
Zhao, W3
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19
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85021781632
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Identification of a Sjogren’s syndrome & susceptibility locus at Oas1 that influences isoform switching, protein expression, and responsiveness to type I interferons
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This study shows that a risk gene variant for pSS affects the transcription of a classical type I IFN-induced gene 2 5 oligoadenylate synthetase 1 (OAS1) and causes reduced protein expression. This could contribute to an increased sensitivity for viral infections in pSS patients
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Li H, Reksten TR, Ice JA, et al. Identification of a Sjogren’s syndrome & susceptibility locus at Oas1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genet 2017; 13:e1006820. This study shows that a risk gene variant for pSS affects the transcription of a classical type I IFN-induced gene - 2’-5’-oligoadenylate synthetase 1 (OAS1) and causes reduced protein expression. This could contribute to an increased sensitivity for viral infections in pSS patients.
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(2017)
PLoS Genet
, vol.13
, pp. e1006820
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Li, H1
Reksten, TR2
Ice, JA3
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20
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84995402666
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Association of interferon-induced helicase C domain (Ifih1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis
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Silva JA, Lima SC, Addobbati C, et al. Association of interferon-induced helicase C domain (Ifih1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis. Genet Mol Res 2016; 15:1–9.
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(2016)
Genet Mol Res
, vol.15
, pp. 1-9
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Silva, JA1
Lima, SC2
Addobbati, C3
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21
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85014020744
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Association of Ifih1 and proinflammatory mediators: potential new clues in SLE-associated pathogenesis
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Munroe ME, Pezant N, Brown MA, et al. Association of Ifih1 and proinflammatory mediators: potential new clues in SLE-associated pathogenesis. PLoS One 2017; 12:e0171193.
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(2017)
PLoS One
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Munroe, ME1
Pezant, N2
Brown, MA3
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22
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84988447167
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Fatigue in primary Sjogren’s syndrome is associated with lower levels of proinflammatory cytokines
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Howard Tripp N, Tarn J, Natasari A, et al. Fatigue in primary Sjogren’s syndrome is associated with lower levels of proinflammatory cytokines. RMD Open 2016; 2:e000282.
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(2016)
RMD Open
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, pp. e000282
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Howard Tripp, N1
Tarn, J2
Natasari, A3
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23
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84983735850
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Nadph oxidase-derived superoxide provides a third signal for Cd4 T cell effector responses
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Padgett LE, Tse HM. Nadph oxidase-derived superoxide provides a third signal for Cd4 T cell effector responses. J Immunol 2016; 197:1733–1742.
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(2016)
J Immunol
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Padgett, LE1
Tse, HM.2
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24
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84938955513
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B-cell epitope spreading and inflammation in a mouse model of arthritis is associated with a deficiency in reactive oxygen species production
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Khmaladze I, Saxena A, Nandakumar KS, Holmdahl R. B-cell epitope spreading and inflammation in a mouse model of arthritis is associated with a deficiency in reactive oxygen species production. Eur J Immunol 2015; 45:2243–2251.
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(2015)
Eur J Immunol
, vol.45
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Khmaladze, I1
Saxena, A2
Nandakumar, KS3
Holmdahl, R.4
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25
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84950147039
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Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation
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Holmdahl R, Sareila O, Olsson LM, et al. Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation. Immunol Rev 2016; 269:228–247.
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(2016)
Immunol Rev
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Holmdahl, R1
Sareila, O2
Olsson, LM3
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26
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85010957414
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A missense variant in Ncf1 is associated with && susceptibility to multiple autoimmune diseases
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&&] show that a genetically determined reduced ROS function is strongly associated with an increased risk for SLE. The articles add new information to the previous reported association between SLE and NCF2 gene variants causing impaired ROS activity
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&&] show that a genetically determined reduced ROS function is strongly associated with an increased risk for SLE. The articles add new information to the previous reported association between SLE and NCF2 gene variants causing impaired ROS activity.
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(2017)
Nat Genet
, vol.49
, pp. 433-437
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Zhao, J1
Ma, J2
Deng, Y3
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27
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85024929994
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A single nucleotide poly- && morphism in the Ncf1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus
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&&] show that a genetically determined reduced ROS function is strongly associated with an increased risk for SLE. The articles add new information to the previous reported association between SLE and NCF2 gene variants causing impaired ROS activity
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&&] show that a genetically determined reduced ROS function is strongly associated with an increased risk for SLE. The articles add new information to the previous reported association between SLE and NCF2 gene variants causing impaired ROS activity.
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(2017)
Ann Rheum Dis
, vol.76
, pp. 1607-1613
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Olsson, LM1
Johansson, AC2
Gullstrand, B3
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28
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85028975317
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Ifn-alpha negatively regulates the expression of endothelial nitric oxide synthase and nitric oxide production: implications for systemic lupus erythematosus
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Buie JJ, Renaud LL, Muise-Helmericks R, Oates JC. Ifn-alpha negatively regulates the expression of endothelial nitric oxide synthase and nitric oxide production: implications for systemic lupus erythematosus. J Immunol 2017; 199:1979–1988.
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(2017)
J Immunol
, vol.199
, pp. 1979-1988
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Buie, JJ1
Renaud, LL2
Muise-Helmericks, R3
Oates, JC.4
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29
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85032581293
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Endothelial dysfunction is associated with activation of the type I interferon system and platelets in patients with systemic lupus erythematosus
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Tyden H, Lood C, Gullstrand B, et al. Endothelial dysfunction is associated with activation of the type I interferon system and platelets in patients with systemic lupus erythematosus. RMD Open 2017; 3:e000508.
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(2017)
RMD Open
, vol.3
, pp. e000508
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Tyden, H1
Lood, C2
Gullstrand, B3
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30
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85016047457
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Siglec1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjogren’s syndrome
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Rose T, Szelinski F, Lisney A, et al. Siglec1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjogren’s syndrome. RMD Open 2016; 2:e000292.
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(2016)
RMD Open
, vol.2
, pp. e000292
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Rose, T1
Szelinski, F2
Lisney, A3
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31
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85024382840
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High maternal expression of siglec1 on & monocytes as a surrogate marker of a type i interferon signature is a risk factor for the development of autoimmune congenital heart block
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This study shows that pregnant women with SSA antibodies and high expression of SIGLEC-1 on monocytes have an increased risk for giving birth to children with autoimmune congenital heart block. The study was small, but suggests that anti-SSA positive patients should be investigated for SIGLEC-1 expression and treated with hydroxychloroquine
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Lisney AR, Szelinski F, Reiter K, et al. High maternal expression of siglec1 on & monocytes as a surrogate marker of a type i interferon signature is a risk factor for the development of autoimmune congenital heart block. Ann Rheum Dis 2017; 76:1476–1480. This study shows that pregnant women with SSA antibodies and high expression of SIGLEC-1 on monocytes have an increased risk for giving birth to children with autoimmune congenital heart block. The study was small, but suggests that anti-SSA positive patients should be investigated for SIGLEC-1 expression and treated with hydroxychloroquine.
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(2017)
Ann Rheum Dis
, vol.76
, pp. 1476-1480
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Lisney, AR1
Szelinski, F2
Reiter, K3
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32
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85028538972
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Plasmacytoid dendritic cells and Rna-containing immune complexes drive expansion of peripheral B cell subsets with an Sle-like phenotype
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Berggren O, Hagberg N, Alexsson A, et al. Plasmacytoid dendritic cells and Rna-containing immune complexes drive expansion of peripheral B cell subsets with an Sle-like phenotype. PLoS One 2017; 12:e0183946.
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(2017)
PLoS One
, vol.12
, pp. e0183946
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Berggren, O1
Hagberg, N2
Alexsson, A3
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33
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84960435612
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A regulatory feedback between & plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus
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This study shows that pDCs from SLE patients promote plasmablast differentiation but fail to induce Breg cells. IFNa could induce the same aberration in cells from healthy individuals. Thus, type I IFN seems to promote a dysregulated pDC and B cell interaction in SLE
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Menon M, Blair PA, Isenberg DA, Mauri C. A regulatory feedback between & plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity 2016; 44:683–697. This study shows that pDCs from SLE patients promote plasmablast differentiation but fail to induce Breg cells. IFNa could induce the same aberration in cells from healthy individuals. Thus, type I IFN seems to promote a dysregulated pDC and B cell interaction in SLE.
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(2016)
Immunity
, vol.44
, pp. 683-697
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Menon, M1
Blair, PA2
Isenberg, DA3
Mauri, C.4
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34
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84958551926
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Association of plasmacytoid dendritic cells with b cell infiltration in minor salivary glands in patients with Sjogren’s syndrome
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Zhao J, Kubo S, Nakayamada S, et al. Association of plasmacytoid dendritic cells with b cell infiltration in minor salivary glands in patients with Sjogren’s syndrome. Mod Rheumatol 2016; 26:716–724.
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(2016)
Mod Rheumatol
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Zhao, J1
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Nakayamada, S3
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35
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85044195662
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Diminished Cxcr5 expression in peripheral blood of patients with Sjogren’s syndrome may relate to both genotype and salivary gland homing
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[Epub ahead of print]
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Aqrawi LA, Ivanchenko M, Bjork A, et al. Diminished Cxcr5 expression in peripheral blood of patients with Sjogren’s syndrome may relate to both genotype and salivary gland homing. Clin Exp Immunol 2018. [Epub ahead of print]
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Clin Exp Immunol
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Aqrawi, LA1
Ivanchenko, M2
Bjork, A3
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36
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68149179247
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Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by dysregulating the Il-23-Th17 pathway
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Espinosa A, Dardalhon V, Brauner S, et al. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by dysregulating the Il-23-Th17 pathway. J Exp Med 2009; 206:1661–1671.
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Espinosa, A1
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37
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85032996263
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The Rna binding protein La/Ss-B promotes Rig-I-mediated Type I and Type III Ifn responses following sendai viral infection
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Mahony R, Broadbent L, Maier-Moore JS, et al. The Rna binding protein La/Ss-B promotes Rig-I-mediated Type I and Type III Ifn responses following sendai viral infection. Sci Rep 2017; 7:14537.
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(2017)
Sci Rep
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, pp. 14537
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Mahony, R1
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Maier-Moore, JS3
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38
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84991665836
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Contrasting expression pattern of Rna-sensing receptors Tlr7, Rig-I and Mda5 in interferon-positive and interferon-negative patients with primary Sjogren’s syndrome
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Maria NI, Steenwijk EC, IJpma AS, et al. Contrasting expression pattern of Rna-sensing receptors Tlr7, Rig-I and Mda5 in interferon-positive and interferon-negative patients with primary Sjogren’s syndrome. Ann Rheum Dis 2017; 76:721–730.
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(2017)
Ann Rheum Dis
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Maria, NI1
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IJpma, AS3
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39
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84991245465
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Plasmacytoid dendritic cells and type 1 interferon promote peripheral expansion of forkhead box protein 3(þ) regulatory T cells specific for the ubiquitous Rna-binding nuclear antigen La/ Sjogren’s syndrome (Ss)-B
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Pan ZJ, Horton CG, Lawrence C, Farris AD. Plasmacytoid dendritic cells and type 1 interferon promote peripheral expansion of forkhead box protein 3(þ) regulatory T cells specific for the ubiquitous Rna-binding nuclear antigen La/ Sjogren’s syndrome (Ss)-B. Clin Exp Immunol 2016; 186:18–29.
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(2016)
Clin Exp Immunol
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, pp. 18-29
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Pan, ZJ1
Horton, CG2
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Farris, AD.4
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40
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Association of increased treg cell levels with elevated indoleamine 2,3-dioxygenase activity and an imbalanced kynurenine pathway in interferon-positive primary Sjogren’s syndrome
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Maria NI, van Helden-Meeuwsen CG, Brkic Z, et al. Association of increased treg cell levels with elevated indoleamine 2,3-dioxygenase activity and an imbalanced kynurenine pathway in interferon-positive primary Sjogren’s syndrome. Arthritis Rheumatol 2016; 68:1688–1699.
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(2016)
Arthritis Rheumatol
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Maria, NI1
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Brkic, Z3
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41
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84958068675
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Genome-wide DNA methylation analysis in multiple tissues in primary Sjogren’s syndrome reveals regulatory effects at interferon-induced genes
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Imgenberg-Kreuz J, Sandling JK, Almlof JC, et al. Genome-wide DNA methylation analysis in multiple tissues in primary Sjogren’s syndrome reveals regulatory effects at interferon-induced genes. Ann Rheum Dis 2016; 75: 2029–2036.
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(2016)
Ann Rheum Dis
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Imgenberg-Kreuz, J1
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42
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85011032592
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Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjogren’s syndrome
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Charras A, Konsta OD, Le Dantec C, et al. Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjogren’s syndrome. Ann Rheum Dis 2017; 76:625–628.
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Ann Rheum Dis
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Charras, A1
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43
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85046670210
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Twin DNA methylation profiling & reveals flare-dependent interferon signature and B-cell promoter hyper-methylation in systemic lupus erythematosus
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Several cell types from monozygotic and dizygotic twins discordant for SLE were investigated with the HumanMethylation450K BeadChip. The majority of differentially methylated genes were hypomethylated and nearly 40 were connected to the IFN pathway. Prominent hypomethylation in IFN-regulated genes were associated to risk for flare
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Ulff-Moller CJ, Asmar F, Liu Y, et al. Twin DNA methylation profiling & reveals flare-dependent interferon signature and B-cell promoter hyper-methylation in systemic lupus erythematosus. Arthritis Rheumatol 2018; 70:878–890. Several cell types from monozygotic and dizygotic twins discordant for SLE were investigated with the HumanMethylation450K BeadChip. The majority of differentially methylated genes were hypomethylated and nearly 40% were connected to the IFN pathway. Prominent hypomethylation in IFN-regulated genes were associated to risk for flare.
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Ulff-Moller, CJ1
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44
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Type I interferons and the cytokine && Tnf cooperatively reprogram the macrophage epigenome to promote inflammatory activation
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The tolerogenic effect of TNF on the TLR3 response by macrophages was abolished by IFNa exposure and this effect was mediated via epigenetic modifications
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Park SH, Kang K, Giannopoulou E, et al. Type I interferons and the cytokine && Tnf cooperatively reprogram the macrophage epigenome to promote inflammatory activation. Nat Immunol 2017; 18:1104–1116. The tolerogenic effect of TNF on the TLR3 response by macrophages was abolished by IFNa exposure and this effect was mediated via epigenetic modifications.
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A phase Ii study of the efficacy and safety of rontalizumab (rhumab interferon-alpha) in patients with systemic lupus erythematosus (Rose)
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Ducreux J, Houssiau FA, Vandepapeliere P, et al. Interferon alpha kinoid induces neutralizing anti-interferon alpha antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon alpha kinoid phase I/Ii study. Rheumatology (Oxford) 2016; 55:1901–1905.
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Anifrolumab, an anti-interferon-alpha & receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus
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This is the first clinical trial with a mAb against the type I IFN receptor in SLE and the study suggests that patients with a high IFN score should be selected for this treatment
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Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an anti-interferon-alpha & receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol 2017; 69:376–386. This is the first clinical trial with a mAb against the type I IFN receptor in SLE and the study suggests that patients with a high IFN score should be selected for this treatment.
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Microglia-dependent synapse loss in type & I interferon-mediated lupus
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Type I IFN can activate microglia to phagocytose synapses, which could be one mechanism behind neuropsychiatric lupus and the observed cognitive dysfunction in many patients
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Jak Inhibitor has the amelioration effect in lupus-prone mice: the involvement of Ifn signature gene downregulation
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Jak inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus
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