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Start Over Author "Abignano G" Journal annals of the rheumatic diseases
41 results on '"Abignano G"'

1. POS1336 MRI DIGITAL ARTERY VOLUME INDEX (DAVIX©) AS QUANTITATIVE, CONTINUOUS IMAGING OUTCOME MEASURE OF VASCULAR DISEASE IN SYSTEMIC SCLEROSIS

Author

Hughes, M., primary, Di Donato, S., additional, Gjeloshi, K., additional, Abignano, G., additional, Danzo, F., additional, Lettieri, G., additional, De Lorenzis, E., additional, Bertham, D., additional, O’connor, P., additional, Kubassova, O., additional, Dehmeshki, J., additional, and Del Galdo, F., additional

Published
2023
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3. POS1267 LONG-TERM SURVEY STUDY OF THE IMPACT OF COVID-19 ON SYSTEMIC AUTOIMMUNE DISEASES. LOW DEATH RATE DESPITE THE INCREASED PREVALENCE OF SYMPTOMATIC INFECTION. ROLE OF PRE-EXISTING INTERSTITIAL LUNG DISEASE AND ONGOING TREATMENTS.

Author

Ferri, C., primary, Raimondo, V., additional, Gragnani, L., additional, Giuggioli, D., additional, Dagna, L., additional, Tavoni, A., additional, Ursini, F., additional, L’andolina, M., additional, Caso, F., additional, Ruscitti, P., additional, Caminiti, M., additional, Foti, R., additional, Riccieri, V., additional, Guiducci, S., additional, Pellegrini, R., additional, Zanatta, E., additional, Varcasia, G., additional, Olivo, D., additional, Gigliotti, P., additional, Cuomo, G., additional, Murdaca, G., additional, Cecchetti, R., additional, De Angelis, R., additional, Romeo, N., additional, Ingegnoli, F., additional, Cozzi, F., additional, Codullo, V., additional, Cavazzana, I., additional, Colaci, M., additional, Abignano, G., additional, De Santis, M., additional, Lubrano, E., additional, Fusaro, E., additional, Spinella, A., additional, Lumetti, F., additional, De Luca, G., additional, Bellando Randone, S., additional, Visalli, E., additional, Dal Bosco, Y., additional, Amato, G., additional, Giannini, D., additional, Bilia, S., additional, Masini, F., additional, Pellegrino, G., additional, Pigatto, E., additional, Generali, E., additional, Pagano Mariano, G., additional, Pettiti, G., additional, Zanframundo, G., additional, Brittelli, R., additional, Aiello, V., additional, Caminiti, R., additional, Scorpiniti, D., additional, Ferrari, T., additional, Campochiaro, C., additional, Brusi, V., additional, Fredi, M., additional, Moschetti, L., additional, Cacciapaglia, F., additional, Ferrari, S. M., additional, DI Cola, I., additional, Vadacca, M., additional, Lorusso, S., additional, Monti, M., additional, Lorini, S., additional, Paparo, S. R., additional, Ragusa, F., additional, Elia, G., additional, Mazzi, V., additional, Aprile, M. L., additional, Tasso, M., additional, Miccoli, M., additional, Bosello, S. L., additional, D’angelo, S., additional, Doria, A., additional, Franceschini, F., additional, Meliconi, R., additional, Matucci-Cerinic, M., additional, Iannone, F., additional, Giacomelli, R., additional, Salvarani, C., additional, Zignego, A. L., additional, Fallahi, P., additional, and Antonelli, A., additional

Published
2022
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4. OP0269 A COMBINED CLINICAL AND BIOMARKER ALGORITHM TO PREDICT FVC DECLINE IN SYSTEMIC SCLEROSIS ASSOCIATED INTERSTITIAL LUNG DISEASE: RESULTS FROM AN INTERNATIONAL MULTICENTRE OBSERVATIONAL COHORT

Author

Hutchinson, M., primary, Abignano, G., additional, Blagojevic, J., additional, Bosello, S. L., additional, Allanore, Y., additional, Denton, C., additional, Distler, O., additional, Emery, P., additional, Matucci-Cerinic, M., additional, and Del Galdo, F., additional

Published
2021
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6. POS1246 COVID-19 IN ITALIAN PATIENTS WITH RHEUMATIC AUTOIMMUNE SYSTEMIC DISEASES: RESULTS OF A NATIONWIDE SURVEY STUDY

Author

Ferri, C., primary, Giuggioli, D., additional, Raimondo, V., additional, Dagna, L., additional, Riccieri, V., additional, Zanatta, E., additional, Guiducci, S., additional, Tavoni, A., additional, Foti, R., additional, Cuomo, G., additional, De Angelis, R., additional, Cozzi, F., additional, Murdaca, G., additional, Cavazzana, I., additional, Romeo, N., additional, Codullo, V., additional, Ingegnoli, F., additional, Pellegrini, R., additional, Varcasia, G., additional, Della Rossa, A., additional, De Santis, M., additional, Abignano, G., additional, Colaci, M., additional, Caminiti, M., additional, L’andolina, M., additional, Lubrano, E., additional, Spinella, A., additional, Lumetti, F., additional, De Luca, G., additional, Bellando Randone, S., additional, Visalli, E., additional, Bilia, S., additional, Masini, F., additional, Pellegrino, G., additional, Pigatto, E., additional, Generali, E., additional, Franceschini, F., additional, Pagano Mariano, G., additional, Barsotti, S., additional, Pettiti, G., additional, Zanframundo, G., additional, Brittelli, R., additional, Aiello, V., additional, Scorpiniti, D., additional, Ferrari, T., additional, Caminiti, R., additional, Campochiaro, C., additional, Gigliotti, P., additional, Cecchetti, R., additional, Olivo, D., additional, Ursini, F., additional, Brusi, V., additional, Meliconi, R., additional, Caso, F., additional, Scarpa, R., additional, D’angelo, S., additional, Iannone, F., additional, Matucci-Cerinic, M., additional, Doria, A., additional, Miccoli, M., additional, Paparo, S. R., additional, Ragusa, F., additional, Elia, G., additional, Ferrari, S. M., additional, Fallahi, P., additional, and Antonelli, A., additional

Published
2021
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16. SAT0229 A Novel Serum Test Based Algorithm To Aid in Very Early Diagnosis of Systemic Sclerosis (VEDOSS)

Author

Blagojevic, J., primary, Abignano, G., additional, Hensor, E.M., additional, Guiducci, S., additional, Bellando Randone, S., additional, Bruni, C., additional, Lepri, G., additional, Romano, E., additional, Mazzotta, C., additional, Calder, N., additional, Messenger, M.P., additional, Buch, M.H., additional, Emery, P., additional, Matucci-Cerinic, M., additional, and Del Galdo, F., additional

Published
2016
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19. SAT0198 The Desscipher Project in Systemic Sclerosis (SSC): Observational Data on Digital Ulcers (DU) Prevention from The Eustar Group

Author

Blagojevic, J., primary, Abignano, G., additional, Allanore, Y., additional, Avouac, J., additional, Cometi, L., additional, Czirják, L., additional, Denton, C., additional, Distler, O., additional, Frerix, M., additional, Guiducci, S., additional, Huscher, D., additional, Jaeger, V.K., additional, Lόránd, V., additional, Maurer, B., additional, Müller-Ladner, U., additional, Nihtyanova, S., additional, Riemekasten, G., additional, Siegert, E., additional, Vettori, S., additional, Walker, U.A., additional, Del Galdo, F., additional, and Matucci-Cerinic, M., additional

Published
2016
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22. SAT0467 The Five Prospective Observational Trials of the International Systemic Sclerosis FP7-Health Research Project Desscipher: A Interim Report

Author

Frerix, M., primary, Abignano, G., additional, Allanore, Y., additional, Avouac, J., additional, Czirják, L., additional, Del Galdo, F., additional, Denton, C., additional, Distler, O., additional, Foeldvari, I., additional, Garay Toth, B., additional, Guiducci, S., additional, Huscher, D., additional, Lόránd, V., additional, Jaeger, V.K., additional, Matucci-Cerinic, M., additional, Maurer, B., additional, Nihtyanova, S., additional, Riemekasten, G., additional, Siegert, E., additional, Tarner, I.H., additional, Valentini, G., additional, Vettori, S., additional, Walker, U.A., additional, and Müller-Ladner, U., additional

Published
2015
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23. FRI0466 Digital Artery Flow Index by Non-Contrast Magnetic Resonance Angiography of the Hand: A Quantitative Outcome Measure of Fibroproliferative Vasculopathy in Raynaud's Phenomenon of Scleroderma

Author

Lettieri, G., primary, Abignano, G., additional, Eng, S., additional, Britton, J., additional, Ridgway, J.P., additional, Evans, R., additional, Rathbone, A., additional, O'Connor, P., additional, Emery, P., additional, Buch, M., additional, and Del Galdo, F., additional

Published
2015
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33. Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study

Author

László Czirják, Brigitte Krummel-Lorenz, Carina Mihai, Serena Fasano, Giuseppina Abignano, Serena Guiducci, Gabriele Valentini, Rosaria Irace, Armando Gabrielli, Francesco Del Galdo, Britta Maurer, Ivan Foeldvari, Ulrich A. Walker, Svetlana I. Nihtyanova, Alessandra Vacca, Dörte Huscher, Ulf Mueller-Ladner, Marc Frerix, Jérôme Avouac, Veronika K. Jaeger, Christopher P. Denton, Oliver Distler, Marco Matucci-Cerinic, Ingo H. Tarner, T. Schmeiser, L. Ananieva, Simona Rednic, Sergey Moiseev, Ana Maria Gherghe, Yannick Allanore, Antonella Riccardi, Elise Siegert, Joerg Henes, Gabriela Riemekasten, Veronika Lóránd, Valentina Messiniti, Valentini, G., Huscher, D., Riccardi, A., Fasano, S., Irace, R., Messiniti, V., Matucci-Cerinic, M., Guiducci, S., Distler, O., Maurer, B., Avouac, J., Tarner, I. H., Frerix, M., Riemekasten, G., Siegert, E., Czirjak, L., Lorand, V., Denton, C. P., Nihtyanova, S., Walker, U. A., Jaeger, V. K., Del Galdo, F., Abignano, G., Ananieva, L. P., Gherghe, A. M., Mihai, C., Henes, J. C., Schmeiser, T., Vacca, A., Moiseev, S., Foeldvari, I., Gabrielli, A., Krummel-Lorenz, B., Rednic, S., Allanore, Y., and Mueller-Ladner, U.

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, preventative role of vasodilator therapy, Vasodilator Agents, Immunology, primary myocardial disease in scleroderma, Vasodilation, General Biochemistry, Genetics and Molecular Biology, Ventricular Function, Left, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Rheumatology, Fibrosis, Internal medicine, medicine, Immunology and Allergy, Humans, Survival analysis, Proportional Hazards Models, 030203 arthritis & rheumatology, Heart Failure, Ejection fraction, Scleroderma, Systemic, Aspirin, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, Arrhythmias, Cardiac, Middle Aged, medicine.disease, 030104 developmental biology, Heart failure, cardiovascular system, Cardiology, Female, Endothelin receptor, business, Cardiomyopathies
Abstract

ObjectivesTo investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) Methods601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5–4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed.ResultsDuring 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF ConclusionsThe present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

Published
2019

34. FRI0241 INFLUENCE OF PATIENT REPORTED ‘’ARTHRITIS ACTIVITY’’ IN DETERMINING SHAQ, HAQ-DI AND COCHIN SCORES IN SYSTEMIC SCLEROSIS

Author

Francesco Masini, Giovanna Cuomo, Anne-Maree Dean, Fiammetta Danzo, G. Abignano, Klodian Gjeloshi, F. Del Galdo, Gjeloshi, K., Danzo, F., Abignano, G., Dean, A. M., Masini, F., Cuomo, G., and Del Galdo, F.

Subjects
medicine.medical_specialty, Rheumatology, business.industry, Internal medicine, Immunology, Immunology and Allergy, Medicine, Arthritis, business, medicine.disease, General Biochemistry, Genetics and Molecular Biology
Abstract

Background:Arthritic involvement in systemic sclerosis (SSc) is a common manifestation impacting on the quality of life. A wide range of articular involvement is recognised including from arthralgia to inflammatory joint and tendon disease.Objectives:To assess the weight of patient reported ‘’arthritis activity’’ in determining Patient Reported Outcome Measures (PROMs) in an observational cohort of SSc patients.Methods:We conducted a retrospective study of 330 clinic episodes from 121 unselected patients diagnosed with SSc according to EULAR/ACR 2013 classification criteria, in annual follow-up (for a total of 165 patients/year) with Pulmonary Function Tests (PFTs), Health Assessment Questionnaire - Disability Index (HAQ-DI), Scleroderma Health Assessment Questionnaire (sHAQ) and Cochin Hand Function Score (CHFS). Hand disability index was assessed by CHFS and global disability index was assessed by HAQ and sHAQ. Patient reported arthritis activity was assessed by Visual Analogical Scale for Arthritis Activity (VAS3). Based on the median of VAS3, patients were classified in two groups and the evaluation of global and hand disability index was performed for each group. Furthermore, we assessed the correlation between the change of VAS3 and the modification of disability scores (ΔHAQ, ΔSHAQ, ΔCHFS) over 12 months of follow-up. Following analysis of distribution, Spearman or Pearson Test were used to determine correlation coefficients, as appropriate (Prism 7).Results:The median disease duration was 5 years (IQR 3-10). The median of VAS3 was 35 (IQR 2 - 66). In patients with VAS3 Conclusion:This analysis of a monocentric non-selected population supports the key role of joint involvement in determining global patient reported functional and hand disability in SSc. Severity of musculoskeletal involvement should be carefully considered when interpreting PROs in patients with SSc.References:[1]Sandler RD, Matucci-Cerinic M, Hughes M. Musculoskeletal hand involvement in systemic sclerosis. Seminars in Arthritis and Rheumatism (2019)Disclosure of Interests:None declared

Published
2020

35. Virtual skin biopsy by optical coherence tomography: the first quantitative imaging biomarker for scleroderma

Author

Concepción Castillo-Gallego, Francesco Del Galdo, Giuseppina Abignano, Paul Emery, Sibel Zehra Aydin, Adam Meekings, Richard J. Wakefield, Vasiliki Liakouli, Dennis McGonagle, Daniel Woods, Abignano, G, Aydin, Sz, Castillo-Gallego, C, Liakouli, V, Woods, D, Meekings, A, Wakefield, Rj, Mcgonagle, Dg, Emery, P, and Del Galdo, F.

Subjects
Male, Pathology, medicine.medical_specialty, genetic structures, Imaging biomarker, Biopsy, Immunology, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Optical coherence tomography, medicine, Immunology and Allergy, Humans, Skin, Scleroderma, Systemic, integumentary system, medicine.diagnostic_test, business.industry, Papillary dermis, Reproducibility of Results, Middle Aged, medicine.disease, Connective tissue disease, Fibrosis, eye diseases, Case-Control Studies, Skin biopsy, Imaging technology, Biomarker (medicine), Female, sense organs, Radiology, business, Tomography, Optical Coherence
Abstract

Skin involvement is of major prognostic value in systemic sclerosis (SSc) and often the primary outcome in clinical trials. Nevertheless, an objective, validated biomarker of skin fibrosis is lacking. Optical coherence tomography (OCT) is an imaging technology providing high-contrast images with 4 μm resolution, comparable with microscopy ('virtual biopsy'). The present study evaluated OCT to detect and quantify skin fibrosis in SSc.We performed 458 OCT scans of hands and forearms on 21 SSc patients and 22 healthy controls. We compared the findings with histology from three skin biopsies and by correlation with clinical assessment of the skin. We calculated the optical density (OD) of the OCT images employing Matlab software and performed statistical analysis of the results, including intraobserver/interobserver reliability, employing SPSS software.Comparison of OCT images with skin histology indicated a progressive loss of visualisation of the dermal-epidermal junction associated with dermal fibrosis. Furthermore, SSc affected skin showed a consistent decrease of OD in the papillary dermis, progressively worse in patients with worse modified Rodnan skin score (p0.0001). Additionally, clinically unaffected skin was also distinguishable from healthy skin for its specific pattern of OD decrease in the reticular dermis (p0.001). The technique showed an excellent intraobserver and interobserver reliability (intraclass correlation coefficient0.8).OCT of the skin could offer a feasible and reliable quantitative outcome measure in SSc. Studies determining OCT sensitivity to change over time and its role in defining skin vasculopathy may pave the way to defining OCT as a valuable imaging biomarker in SSc.

Published
2013

36. Broad clinical spectrum of SARS-CoV-2-associated inflammatory joint disease in adults: a report of 35 cases from the COVID-19 & Autoimmune Systemic Disease Italian study group.

Author

Ursini F, Ruscitti P, D'Angelo S, Cacciapaglia F, De Angelis R, Campochiaro C, Caso F, De Santis M, Di Cola I, Parisi S, Raimondo V, Abignano G, Costa L, Ciaffi J, Dagna L, Iagnocco A, Iannone F, Meliconi R, Giacomelli R, and Ferri C

Subjects
Adult, Aged, Female, Humans, Italy, Male, Middle Aged, SARS-CoV-2, Arthritis epidemiology, Arthritis virology, COVID-19 complications
Abstract

Competing Interests: Competing interests: None declared.

Published
2021
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37. Long non-coding RNA HOTAIR drives EZH2-dependent myofibroblast activation in systemic sclerosis through miRNA 34a-dependent activation of NOTCH.

Author

Wasson CW, Abignano G, Hermes H, Malaab M, Ross RL, Jimenez SA, Chang HY, Feghali-Bostwick CA, and Del Galdo F

Subjects
Amyloid Precursor Protein Secretases antagonists & inhibitors, Epigenesis, Genetic, Fibrosis, Histone Code, Humans, Indoles pharmacology, Phenotype, Pyridones pharmacology, Receptors, Notch antagonists & inhibitors, Scleroderma, Systemic genetics, Scleroderma, Systemic pathology, Signal Transduction, Skin cytology, Skin metabolism, Skin pathology, Enhancer of Zeste Homolog 2 Protein metabolism, Fibroblasts metabolism, MicroRNAs metabolism, Myofibroblasts metabolism, RNA, Long Noncoding metabolism, Receptors, Notch metabolism, Scleroderma, Systemic metabolism
Abstract

Background: Systemic sclerosis (SSc) is characterised by autoimmune activation, tissue and vascular fibrosis in the skin and internal organs. Tissue fibrosis is driven by myofibroblasts, that are known to maintain their phenotype in vitro, which is associated with epigenetically driven trimethylation of lysine 27 of histone 3 (H3K27me3)., Methods: Full-thickness skin biopsies were surgically obtained from the forearms of 12 adult patients with SSc of recent onset. Fibroblasts were isolated and cultured in monolayers and protein and RNA extracted. HOX transcript antisense RNA (HOTAIR) was expressed in healthy dermal fibroblasts by lentiviral induction employing a vector containing the specific sequence. Gamma secretase inhibitors were employed to block Notch signalling. Enhancer of zeste 2 (EZH2) was blocked with GSK126 inhibitor., Results: SSc myofibroblasts in vitro and SSc skin biopsies in vivo display high levels of HOTAIR, a scaffold long non-coding RNA known to direct the histone methyltransferase EZH2 to induce H3K27me3 in specific target genes. Overexpression of HOTAIR in dermal fibroblasts induced EZH2-dependent increase in collagen and α-SMA expression in vitro, as well as repression of miRNA-34A expression and consequent NOTCH pathway activation. Consistent with these findings, we show that SSc dermal fibroblast display decreased levels of miRNA-34a in vitro. Further, EZH2 inhibition rescued miRNA-34a levels and mitigated the profibrotic phenotype of both SSc and HOTAIR overexpressing fibroblasts in vitro., Conclusions: Our data indicate that the EZH2-dependent epigenetic phenotype of myofibroblasts is driven by HOTAIR and is linked to miRNA-34a repression-dependent activation of NOTCH signalling., Competing Interests: Competing interests: H.Y.C. is a co-founder of Accent Therapeutics, Boundless Bio, and advisor to 10x Genomics, Arsenal Biosciences, and Spring Discovery., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2020
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38. Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study.

Author

Valentini G, Huscher D, Riccardi A, Fasano S, Irace R, Messiniti V, Matucci-Cerinic M, Guiducci S, Distler O, Maurer B, Avouac J, Tarner IH, Frerix M, Riemekasten G, Siegert E, Czirják L, Lóránd V, Denton CP, Nihtyanova S, Walker UA, Jaeger VK, Del Galdo F, Abignano G, Ananieva LP, Gherghe AM, Mihai C, Henes JC, Schmeiser T, Vacca A, Moiseev S, Foeldvari I, Gabrielli A, Krummel-Lorenz B, Rednic S, Allanore Y, and Müeller-Ladner U

Subjects
Adult, Arrhythmias, Cardiac epidemiology, Arrhythmias, Cardiac etiology, Arrhythmias, Cardiac prevention & control, Cardiomyopathies etiology, Female, Heart Failure epidemiology, Heart Failure etiology, Heart Failure prevention & control, Humans, Incidence, Male, Middle Aged, Proportional Hazards Models, Scleroderma, Systemic physiopathology, Ventricular Dysfunction, Left epidemiology, Ventricular Dysfunction, Left etiology, Ventricular Dysfunction, Left prevention & control, Ventricular Function, Left drug effects, Aspirin administration & dosage, Cardiomyopathies epidemiology, Cardiomyopathies prevention & control, Scleroderma, Systemic complications, Vasodilator Agents therapeutic use
Abstract

Objectives: To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc)., Methods: 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed., Results: During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05)., Conclusions: The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2019
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39. Scleroderma fibroblasts suppress angiogenesis via TGF-β/caveolin-1 dependent secretion of pigment epithelium-derived factor.

Author

Liakouli V, Elies J, El-Sherbiny YM, Scarcia M, Grant G, Abignano G, Derrett-Smith EC, Esteves F, Cipriani P, Emery P, Denton CP, Giacomelli R, Mavria G, and Del Galdo F

Subjects
Animals, Cells, Cultured, Endothelial Cells metabolism, Female, Humans, Immunohistochemistry, Male, Mice, Mice, Transgenic, Real-Time Polymerase Chain Reaction, Scleroderma, Systemic metabolism, Skin pathology, Caveolin 1 metabolism, Eye Proteins metabolism, Fibroblasts metabolism, Neovascularization, Pathologic metabolism, Nerve Growth Factors metabolism, Scleroderma, Systemic pathology, Serpins metabolism, Transforming Growth Factor beta metabolism
Abstract

Objectives: Systemic sclerosis (SSc) is characterised by tissue fibrosis and vasculopathy with defective angiogenesis. Transforming growth factor beta (TGF-β) plays a major role in tissue fibrosis, including downregulation of caveolin-1 (Cav-1); however, its role in defective angiogenesis is less clear. Pigment epithelium-derived factor (PEDF), a major antiangiogenic factor, is abundantly secreted by SSc fibroblasts. Here, we investigated the effect of TGF-β and Cav-1 on PEDF expression and the role of PEDF in the ability of SSc fibroblasts to modulate angiogenesis., Methods: PEDF and Cav-1 expression in fibroblasts and endothelial cells were evaluated by means of immunohistochemistry on human and mouse skin biopsies. PEDF and Cav-1 were silenced in cultured SSc and control fibroblasts using lentiviral short-hairpin RNAs. Organotypic fibroblast-endothelial cell co-cultures and matrigel assays were employed to assess angiogenesis., Results: PEDF is highly expressed in myofibroblasts and reticular fibroblasts with low Cav-1 expression in SSc skin biopsies, and it is induced by TGF-β in vitro. SSc fibroblasts suppress angiogenesis in an organotypic model. This model is reproduced by silencing Cav-1 in normal dermal fibroblasts. Conversely, silencing PEDF in SSc fibroblasts rescues their antiangiogenic phenotype. Consistently, transgenic mice with TGF-β receptor hyperactivation show lower Cav-1 and higher PEDF expression levels in skin biopsies accompanied by reduced blood vessel density., Conclusions: Our data reveal a new pathway by which TGF-β suppresses angiogenesis in SSc, through decreased fibroblast Cav-1 expression and subsequent PEDF secretion. This pathway may present a promising target for new therapeutic interventions in SSc., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Published
2018
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40. The enhanced liver fibrosis test: a clinical grade, validated serum test, biomarker of overall fibrosis in systemic sclerosis.

Author

Abignano G, Cuomo G, Buch MH, Rosenberg WM, Valentini G, Emery P, and Del Galdo F

Subjects
Adult, Aged, Autoantibodies blood, Biomarkers blood, Cross-Sectional Studies, Disability Evaluation, Female, Fibrosis diagnosis, Fibrosis etiology, Humans, Liver Cirrhosis etiology, Male, Middle Aged, Myocardium pathology, Pulmonary Diffusing Capacity physiology, Pulmonary Fibrosis diagnosis, Pulmonary Fibrosis etiology, Scleroderma, Systemic immunology, Scleroderma, Systemic physiopathology, Severity of Illness Index, Skin pathology, Liver Cirrhosis diagnosis, Scleroderma, Systemic complications
Abstract

Objectives: The absence of a serological surrogate outcome measure of fibrosis in systemic sclerosis (SSc) is a major deficiency for intervention studies and clinical management. An algorithm including the serum concentration of procollagen-III aminoterminal-propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid, has recently been validated as predictive of severity and clinical outcome in chronic liver diseases (enhanced liver fibrosis (ELF) test) and implemented as a clinical grade test available for physicians. We evaluated the ELF test as a surrogate outcome measure in SSc., Methods: The ELF score was determined blindly in 210 patients with SSc. Results were correlated with clinical, functional and instrumental variables including disease severity, activity and disability., Results: The ELF test was above normal range in 83% of SSc patients (175/210). The ELF score showed a significant correlation (p<0.0001) with extent of skin involvement (r=0.28), diffusing lung capacity of carbon monoxide (DLCO) (r=-0.32), health assessment questionnaire-disability index (HAQ-DI) (r=0.32), disease severity score (r=0.3) and age (r=0.41). In addition, ELF correlated with disease activity (r=0.23; p=0.02). Using regression analysis, the extent of skin involvement, age, DLCO and gender were independently associated with the ELF score. The ELF score did not correlate with the presence of pulmonary artery hypertension, digital ulcers or any other measure of vasculopathy., Conclusions: The ELF test is a clinical-grade serum test that significantly correlates with several measures of fibrosis in SSc and with overall disease activity, severity and HAQ-DI. The specific correlation with fibrosis and its face validity, together with the feasibility of the test, warrant its further development as a surrogate outcome measure of fibrosis in SSc.

Published
2014
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41. Virtual skin biopsy by optical coherence tomography: the first quantitative imaging biomarker for scleroderma.

Author

Abignano G, Aydin SZ, Castillo-Gallego C, Liakouli V, Woods D, Meekings A, Wakefield RJ, McGonagle DG, Emery P, and Del Galdo F

Subjects
Biopsy, Case-Control Studies, Female, Fibrosis, Humans, Male, Middle Aged, Reproducibility of Results, Scleroderma, Systemic diagnosis, Scleroderma, Systemic pathology, Skin pathology, Tomography, Optical Coherence methods
Abstract

Background: Skin involvement is of major prognostic value in systemic sclerosis (SSc) and often the primary outcome in clinical trials. Nevertheless, an objective, validated biomarker of skin fibrosis is lacking. Optical coherence tomography (OCT) is an imaging technology providing high-contrast images with 4 μm resolution, comparable with microscopy ('virtual biopsy'). The present study evaluated OCT to detect and quantify skin fibrosis in SSc., Methods: We performed 458 OCT scans of hands and forearms on 21 SSc patients and 22 healthy controls. We compared the findings with histology from three skin biopsies and by correlation with clinical assessment of the skin. We calculated the optical density (OD) of the OCT images employing Matlab software and performed statistical analysis of the results, including intraobserver/interobserver reliability, employing SPSS software., Results: Comparison of OCT images with skin histology indicated a progressive loss of visualisation of the dermal-epidermal junction associated with dermal fibrosis. Furthermore, SSc affected skin showed a consistent decrease of OD in the papillary dermis, progressively worse in patients with worse modified Rodnan skin score (p<0.0001). Additionally, clinically unaffected skin was also distinguishable from healthy skin for its specific pattern of OD decrease in the reticular dermis (p<0.001). The technique showed an excellent intraobserver and interobserver reliability (intraclass correlation coefficient >0.8)., Conclusions: OCT of the skin could offer a feasible and reliable quantitative outcome measure in SSc. Studies determining OCT sensitivity to change over time and its role in defining skin vasculopathy may pave the way to defining OCT as a valuable imaging biomarker in SSc.

Published
2013
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