scholarly journals A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

2012 ◽  
Vol 14 (2) ◽  
pp. R85 ◽  
Author(s):  
Lara Bossini-Castillo ◽  
Carmen P Simeon ◽  
Lorenzo Beretta ◽  
Jasper C Broen ◽  
Madelon C Vonk ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Multicenter Study ◽  
Gene Association ◽  
Cd226 Gene

AB0987 Quantification of Interstitial Pulmonary Fibrosis in Systemic Sclerosis Using an Open-Source DICOM Software (OSIRIX)

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 1127.1-1127
Author(s):  
M. Carotti ◽  
F. Salaffi ◽  
S. Bosello ◽  
A. Ciapetti ◽  
E. Bichisecchi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Open Source ◽  
Interstitial Pulmonary Fibrosis

scholarly journals OP0242 EFFECTS OF THE AUTOTAXIN INHIBITOR ZIRITAXESTAT ON SKIN AND LUNG FIBROSIS IN A MURINE GRAFT-VERSUS-HOST DISEASE MODEL OF SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 148.1-149
Author(s):  
Y. Zhang ◽  
L. Summa ◽  
B. Heckmann ◽  
J. H. W. Distler
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Graft Versus Host Disease ◽  
Murine Model ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Dermal Thickness ◽  
Disease Modifying

Background:There is an unmet medical need for new drugs to treat systemic sclerosis (SSc). Autotaxin (ATX) is a widely expressed enzyme that regulates diverse cellular processes, including proliferation, differentiation and migration, and has been implicated in the pathogenesis of SSc. Targeting ATX is a promising new strategy for treating SSc. The autotaxin inhibitor ziritaxestat (GLPG1690) is a potential first-in-class disease-modifying drug for SSc that has been shown to improve skin score in the Phase 2a NOVESA (NCT03798366) trial in patients with SSc.Objectives:To investigate the effects of ziritaxestat in a chronic graft-versus-host disease (cGvHD) murine model of SSc.Methods:Effects of ziritaxestat (10 or 30 mg/kg twice daily [bid]) on disease activity were assessed in a cGvHD murine model of SSc (allogeneic bone marrow transplantation [BMT] with B10.D2 donor and BALB/c recipient; syngeneic mice as controls). Ziritaxestat or nintedanib (60 mg/kg once daily [qd]) as active comparator was administered 21 d after BMT and continued for 35 d. Effects of ziritaxestat were assessed by clinical monitoring, histologic assessment of skin and lungs (dermal thickness, Ashcroft scores and collagen-covered area), immunofluorescence staining with Trichrome and Sirius Red for myofibroblasts, and biochemical analysis of collagen content, as measured by hydroxyproline levels.Results:Ziritaxestat 30 mg/kg bid for 35 days significantly reduced the clinical cutaneous score in the murine cGvHD model by 57% (p<0.05) compared with vehicle, and to a similar extent when compared with nintedanib 60 mg/kg (38%; p<0.05). Dermal accumulation of collagen and dermal thickness (Figure) were reduced with ziritaxestat 10 and 30 mg/kg compared with vehicle. At 30 mg/kg, ziritaxestat reversed the increase in the allogeneic model (p<0.001), returning dermal thickness to the levels in non-fibrotic control mice. Ziritaxestat also significantly reduced pulmonary fibrosis in the cGvHD model, with reductions in the fibrotic lung area (ziritaxestat 10 and 30 mg/kg; p<0.001 for both) and Ashcroft scores (ziritaxestat 30 mg/kg; p<0.05). Ziritaxestat was generally well tolerated.Conclusion:Ziritaxestat improved the histological, biochemical and clinical symptom readouts of dermal and pulmonary fibrosis in a murine model, consistent with a broad and rapid disease-modifying effect in SSc.Acknowledgements:This study was funded by Galapagos NV (Mechelen, Belgium). Medical writing/editorial support was provided by Ian Faulkner, PhD (Aspire Scientific, Bollington, UK) funded by Galapagos NV.Disclosure of Interests:Yun Zhang Employee of: 4D Science, Lena Summa Employee of: 4D Science, Bertrand Heckmann Shareholder of: Galapagos, Employee of: Galapagos, Jörg H.W. Distler Shareholder of: 4D Science, Consultant of: Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, Bristol Myers Squibb, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, Novartis, Sanofi-Aventis, RedX and UCB

Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis

The Lancet ◽  
1991 ◽  
Vol 338 (8775) ◽  
pp. 1152 ◽  
Author(s):  
M Vanoli ◽  
S Della Bella ◽  
C Coppola ◽  
N Eisera ◽  
R Scorza
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis

scholarly journals Correction: Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis

2014 ◽  
Vol 16 (2) ◽  
pp. 406
Author(s):  
Gianluca Bagnato ◽  
Alessandra Bitto ◽  
Natasha Irrera ◽  
Gabriele Pizzino ◽  
Donatella Sangari ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Murine Model ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Correlation between Serum Krebs von den Lungen-6 Levels with Forced Vital Capacity and Modified Rodnan Skin Score of Patients with Restrictive Lung Disease in Diffuse-Type Systemic Sclerosis

2019 ◽  
Vol 11 (2) ◽  
Author(s):  
Herlina Yani ◽  
Sumartini Dewi ◽  
Andri Reza Rahmadi
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Skin Fibrosis ◽  
Diffuse Type ◽  
Skin Score ◽  
Restrictive Lung Disease ◽  
Modified Rodnan Skin Score

Background Pulmonary fibrosis / intersitial lung disease (ILD) in systemic sclerosis (SSc) is a complicated restrictive pulmonary disease and the leading cause of disease-related mortality. Progressive skin fibrosis in diffuse-type SSc (dSSc) is associated with decreased forced vital capacity (FVC). Modified Rodnan Skin Score (mRSS) examination is used as a parameter to assess skin fibrosis, while high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are used to assess pulmonary fibrosis. The HRCT test remains as the gold standard in diagnosing ILD. However, it costs a lot and is not available in all healthcare facilities. Krebs Von den Lungen-6 (KL-6) is a biomarker to evaluate pulmonary fibrosis. The aim of this study was to analyze the correlation of serum KL-6 levels with FVC and mRSS value of patients with restrictive lung disease in dSSc. Method This was a cross-sectional study that used primary data from dSSc patients who visited rheumatology outpatient clinic in Hasan Sadikin Hospital Bandung, Indonesia, during the period of June-July 2019. History taking, physical examination, mRSS, spirometry, and serum KL-6 levels were performed. Data were analyzed using the Rank Spearman correlation test.  Result There were 27 subjects with the mean age of 42 ± 12 years. Based on FVC (%) restrictive lung disease criteria, the majority of subjects (74.1%) had severe restrictive lung disease and the rest of all subjects (25.9%) were non severe restrictive lung disease. Serum KL-6 levels ranged from 0.545 to 8.138 ng/ml. The results showed that there was no correlation between serum KL-6 levels and FVC values (r = -0.118, p = 0.279) and mRSS (r = 0.101, p = 0.312 ). Conclusion There is no correlation between serum KL-6 levels with FVC and mRSS value of patient with restritive lung disease in diffuse type systemic sclerosis. Keywords : diffuse type systemic sclerosis, Forced Vital Capacity, KL-6, mRSS, restrictive lung disease.      

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