A potential contribution of decreased serum galectin‐10 levels to systemic inflammation and pulmonary vascular involvement in systemic sclerosis

2021 ◽  
Author(s):  
Kentaro Awaji ◽  
Takuya Miyagawa ◽  
Yuki Fukui ◽  
Satoshi Toyama ◽  
Jun Omatsu ◽  
...  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Sayonara Maria Calado Gonçalves ◽  
Anderson Rodrigues de Almeida ◽  
Rafaela Silva Guimarães Gonçalves ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
...  

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1600.2-1600
Author(s):  
S. Sciacca ◽  
C. Rotondo ◽  
A. Corrado ◽  
L. Giardullo ◽  
S. Stefania ◽  
...  

Background:Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Myocardial calcifications have been related with cardiovascular diseases (CVD) such as focal wall motion abnormalities and arrhythmias. The impact of vascular calcifications is under investigation in order to define the risk of cardiovascular events. The relationship between cardiac calcification and systemic sclerosis (SSc) has not been investigated.Objectives:The aim of the study is to evaluate the frequency of different patterns of cardiac calcification in SSc patients, and to correlate them to other CVD risk factors.Methods:We analyzed thoracic-CT scanners of 35 SSc patients (88% female, aged 47,8 ys ±12,9, disease duration 12,8 ys ±9) to determine the location and extension of vascular and cardiac calcification. All recruited patients fulfilled the 2013 ACR-EULAR classification criteria for SSc. No one patients had renal failure, cardiomyopathy, myocarditis, history of cardiac surgery or radiotherapy.Results:We found myocardial vessels calcifications (MCv) in 37% SSc patients, aortic wall calcifications (ACw)in 60% SSc patients, cardiac valve calcifications (VC) in 28% SSc patient and heart wall calcifications (HCw) in 20%.The SSc patients with almost one calcification had older age (65±9,8 ys vs 50±8,8 ys; p=0,0001) and higher values of circulating NTproBNP (336,9±351,9 vs 144,2±107,8; p=0,04) compared to those without.In particular, the SSc patients with MCv had and uric acid (5,3 ±1,5 vs 4,1 ±1,3; p=0,05), higher rate of PAH (25% vs 0%; p=0,037), arrhythmia (38,5% vs 9%; p=0,036) and higher prevalence of CENP-B antibodies(46% vs 4%; p=0,01) compared to patients without MCv.Patients with HCw had lower C reactive protein (0,16 ±0,10 vs 0,7±0,7; p=0,008) compared to those without HCw. No differences in the rate of heart and vascular complications of SSc were observed.The SSc patients with ACw had higher frequency of arrhythmia (33% vs 0%; p=0,016) and longer disease duration (15,5 y ±9,9 vs 8,8 ±5,8; p=0,03).The SSc patients with VC had higher rate of PAH (33%vs0%; p=0,003) and uric acid (6±0,5vs3,8±1,2 p=0,0001).Regression analysis excluded any association with gender, BMI, systemic arterial hypertension, steroid therapy, hypovitaminosis D or smoke habit. No cardiovascular event was recorded in one year of observation.Conclusion:All patterns of calcifications may be related mostly with the older age. Myocardial vessels calcifications have been found in a high percentage of SSc patients and in particular in those with PAH and positive for anti CENP-B. Furthermore, myocardial vessels calcifications could be associated to the higher occurrence of arrhythmia. More studied are needed to assess the importance of vascular calcification as a part of the vascular involvement in SSc.References:[1]John W. Nance Jr. MD. Myocardial calcifications: Pathophysiology, etiologies, differential diagnoses, and imaging findings. Journal of Cardiovascular Computed Tomography 9 (2015) 58 e 67.[2]Pagkopoulou E, Poutakidou M. Cardiovascular risk in systemic sclerosis: Micro- and Macro-vascular involvement. Indian J Rheumatol 2017;12, Suppl S1:211-7[3]Plastiras SC, Toumanidis ST. Systemic sclerosis: the heart of the matter. Hellenic J Cardiol. 2012;53(4):287–300.Disclosure of Interests:None declared


2020 ◽  
Vol 9 (11) ◽  
pp. 3388
Author(s):  
Akira Utsunomiya ◽  
Noritaka Oyama ◽  
Minoru Hasegawa

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by dysregulation of the immune system, vascular damage, and fibrosis of the skin and internal organs. Patients with SSc show a heterogeneous phenotype and a range of clinical courses. Therefore, biomarkers that are helpful for precise diagnosis, prediction of clinical course, and evaluation of the therapeutic responsiveness of disease are required in clinical practice. SSc-specific autoantibodies are currently used for diagnosis and prediction of clinical features, as other biomarkers have not yet been fully vetted. Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and CCL18 have been considered as serum biomarkers of SSc-related interstitial lung disease. Moreover, levels of circulating brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) can provide diagnostic information and indicate the severity of pulmonary arterial hypertension. Assessment of several serum/plasma cytokines, chemokines, growth factors, adhesion molecules, and other molecules may also reflect the activity or progression of fibrosis and vascular involvement in affected organs. Recently, microRNAs have also been implicated as possible circulating indicators of SSc. In this review, we focus on several potential SSc biomarkers and discuss their clinical utility.


2019 ◽  
Vol 28 (5) ◽  
pp. 536-542 ◽  
Author(s):  
Ryosuke Saigusa ◽  
Takashi Yamashita ◽  
Shunsuke Miura ◽  
Megumi Hirabayashi ◽  
Kouki Nakamura ◽  
...  

2017 ◽  
Vol 44 (8) ◽  
pp. 1198-1205 ◽  
Author(s):  
Takashi Taniguchi ◽  
Yoshihide Asano ◽  
Kouki Nakamura ◽  
Takashi Yamashita ◽  
Ryosuke Saigusa ◽  
...  

Objective.CXCL6, a chemokine with proangiogenic property, is reported to be involved in vasculopathy associated with systemic sclerosis (SSc). We investigated the contribution of CXCL6 to SSc development by focusing on the association of friend leukemia virus integration 1 (Fli1) deficiency, a potential predisposing factor of SSc, with CXCL6 expression and clinical correlation of serum CXCL6 levels.Methods.mRNA levels of target genes and the binding of Fli1 to the CXCL6 promoter were evaluated by quantitative reverse transcription-PCR and chromatin immunoprecipitation, respectively. Serum CXCL6 levels were determined by ELISA.Results.FLI1 siRNA significantly enhanced CXCL6 mRNA expression in human dermal fibroblasts and human dermal microvascular endothelial cells, while Fli1 haploinsufficiency significantly suppressed CXCL6 mRNA expression in murine peritoneal macrophages stimulated with lipopolysaccharide. Supporting a critical role of Fli1 deficiency to induce SSc-like phenotypes, CXCL6 mRNA expression was higher in SSc dermal fibroblasts than in normal dermal fibroblasts. Importantly, Fli1 bound to the CXCL6 promoter in dermal fibroblasts, endothelial cells, and THP-1 cells. In patients with SSc, serum CXCL6 levels correlated positively with the severity of dermal and pulmonary fibrosis and were elevated in association with cardiac and pulmonary vascular involvement and cutaneous vascular symptoms, including Raynaud phenomenon, digital ulcers (DU)/pitting scars, and telangiectasia. Especially, serum CXCL6 levels were associated with DU/pitting scars and heart involvement by multiple regression analysis.Conclusion.CXCL6 expression is upregulated by Fli1 deficiency in fibroblasts and endothelial cells, potentially contributing to the development of fibrosis and vasculopathy in the skin, lung, and heart of SSc.


2007 ◽  
Vol 56 (8) ◽  
pp. 2747-2754 ◽  
Author(s):  
Y. Allanore ◽  
R. Seror ◽  
A. Chevrot ◽  
A. Kahan ◽  
J. L. Drapé

2012 ◽  
Vol 46 (10) ◽  
pp. 1439-1439 ◽  
Author(s):  
Rebeca Iglesias Barreira ◽  
Belén Bardán García ◽  
Mónica Granero López ◽  
Iria Rodríguez Legazpi ◽  
Hortensia Álvarez Díaz ◽  
...  

Objective TO report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. Case Summary In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5–1 ng/kg/min (6 hours per day, for 5 days every 6–8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Discussion Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. Conclusions This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.


2010 ◽  
Vol 39 (1) ◽  
pp. 63-70 ◽  
Author(s):  
H Harðardóttir ◽  
HAC van Helvoort ◽  
MC Vonk ◽  
FHJ van den Hoogen ◽  
PNR Dekhuijzen ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document