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Your search keyword '"RNA Polymerase III/immunology"' showing total 4 results
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4 results on '"RNA Polymerase III/immunology"'

1. Treatment outcome in early diffuse cutaneous systemic sclerosis:the European Scleroderma Observational Study (ESOS)

Abstract

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.TRIAL REGISTRATION NUMBER: NCT02339441.

Published
2017

2. Treatment outcome in early diffuse cutaneous systemic sclerosis:the European Scleroderma Observational Study (ESOS)

Abstract

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.TRIAL REGISTRATION NUMBER: NCT02339441.

Published
2017

3. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

Author

Herrick, A, Pan, X, Peytrignet, S, Lunt, M, Hesselstrand, R, Mouthon, L, Silman, A, Brown, E, Czirják, L, Distler, J, Distler, O, Fligelstone, K, Gregory, W, Ochiel, R, Vonk, M, Ancuţa, C, Ong, V, Farge, D, Hudson, M, Matucci-Cerinic, M, Balbir-Gurman, A, Midtvedt, Ø, Jordan, A, Jobanputra, P, Stevens, W, Moinzadeh, P, Hall, F, Agard, C, Anderson, M, Diot, E, Madhok, R, Akil, M, Buch, M, Chung, L, Damjanov, N, Gunawardena, H, Lanyon, P, Ahmad, Y, Chakravarty, K, Jacobsen, S, Macgregor, A, McHugh, N, Müller-Ladner, U, Riemekasten, G, Becker, M, Roddy, J, Carreira, P, Fauchais, A, Hachulla, E, Hamilton, J, İnanç, M, McLaren, J, Van Laar, J, Pathare, S, Proudman, S, Rudin, A, Sahhar, J, Coppere, B, Serratrice, C, Sheeran, T, Veale, D, Grange, C, Trad, G, and Denton, C

Subjects
Adult, Male, Methotrexate/therapeutic use, RNA Polymerase III/immunology, Antibodies, Antinuclear/immunology, Systemic Sclerosis, Severity of Illness Index, Cohort Studies, Early Medical Intervention, Journal Article, Humans, Prospective Studies, Cyclophosphamide, Autoantibodies, Nuclear Proteins, RNA Polymerase III, Mycophenolic Acid/therapeutic use, Clinical and Epidemiological Research, Middle Aged, Mycophenolic Acid, Scleroderma, Diffuse/drug therapy, Treatment, Europe, Survival Rate, Methotrexate, Treatment Outcome, DNA Topoisomerases, Type I, Cyclophosphamide/therapeutic use, Antibodies, Antinuclear, Scleroderma, Diffuse, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Immunosuppressive Agents/therapeutic use, Nuclear Proteins/immunology, Female, Autoantibodies/immunology, Immunosuppressive Agents
Abstract

Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or ‘no immunosuppressant’. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: −4.0 (−5.2 to −2.7) units for methotrexate, −4.1 (−5.3 to −2.9) for MMF, −3.3 (−4.9 to −1.7) for cyclophosphamide and −2.2 (−4.0 to −0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. Trial Registration Number: NCT02339441.

Published
2017

4. Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

Author

Roger Hesselstrand, Niels Hh Heegaard, Gabriel N. Teku, Samantha O. Steen, Anting Liu Carlsen, Marie Wildt, Dirk M. Wuttge, and Mauno Vihinen

Subjects
Male, Adult, Pathology, medicine.medical_specialty, systemic sclerosis, RNA Polymerase III/immunology, systemic sclerosis scleroderma micro-RNA autoantibody plasma GLOMERULAR-FILTRATION-RATE LUPUS-ERYTHEMATOSUS EXPRESSION CLASSIFICATION SCLERODERMA, Disease, Systemic scleroderma, Scleroderma, Rheumatology, RNA, Small Nuclear, Scleroderma, Systemic/blood, microRNA, medicine, Humans, scleroderma, Pharmacology (medical), skin and connective tissue diseases, plasma, Autoantibodies, Aged, Rheumatology and Autoimmunity, DNA Topoisomerases, Type I/immunology, Sweden, Scleroderma, Systemic, RNA, Small Nuclear/immunology, integumentary system, business.industry, micro-RNA, Autoantibody, RNA Polymerase III, MicroRNAs/blood, Middle Aged, medicine.disease, Phenotype, MicroRNAs, Cross-Sectional Studies, DNA Topoisomerases, Type I, Immunology, Regression Analysis, Female, Autoantibodies/blood, business, autoantibody
Abstract

Objective. To evaluate the expression profiles of cell-free plasma miRNAs in SSc and to characterize their correlation with disease subgroups (lcSSc and dcSSc) and with autoantibody profiles.Methods. Using quantitative RT-PCR, the abundance of 45 mature miRNAs in plasma was determined in 95 patients (lcSSc = 63; dcSSc = 32), representing the following autoantibody subgroups: ACA, anti-DNA topoisomerase I, anti-RNA polymerase III and anti-U1-ribonucleoprotein. MiRNA data were correlated with clinical and paraclinical data. Multiple regression was used to model membership of the lcSSc, dcSSc and autoantibody subgroups, based on miRNA expression profiles.Results. Thirty-six miRNAs were measurable in all samples. Four (miRNA-223, -181b, -342-3p and -184) were differently expressed in lcSSc and dcSSc (false discovery rate < 0.05). Ten miRNAs exhibited statistically significantly different levels in one or more autoantibody groups, and five (miRNA-409, -184, -92a, -29a and -101) remained significant after correction for multiple comparisons. Multiple regression models accurately predicted ACA and anti-DNA topoisomerase I antibody-positive patients (area under the curve (AUC) = 0.97 and 0.93, respectively) as well as membership of the dcSSc and lcSSc groups (AUC = 0.88).Conclusion. Circulating miRNA profiles differ between lcSSc and dcSSc patients and between patients with different autoantibodies. This is the first time autoantibody profiles, disease phenotypes and plasma miRNA profiles have been shown to correlate in an autoimmune disease. The data support a pathobiological role of miRNAs because specific miRNAs associate with autoantibody profiles of known diagnostic and prognostic value.

Published
2015

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