scholarly journals A PILOT STUDY ON SOLUBLE (PRO)RENIN RECEPTOR IN SYSTEMIC SCLEROSIS

2015 ◽  
Vol 24 (2) ◽  
pp. 108-113
Author(s):  
Marilena Gorga ◽  
◽  
Alina-Mihaela Soare ◽  
Ana-Maria Gherghe ◽  
Rucsandra Dobrota ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pilot Study ◽  
Wnt Signaling ◽  
Angiotensin Receptor Blockers ◽  
Severe Disease ◽  
Serum Levels ◽  
Digital Ulcers ◽  
Serum Samples ◽  
Reported Data ◽  
Spearman Test

Background. Wnt signaling is involved in fibrosis, but the mechanisms of cross-talk with other pathways, like TGF-β, are not fully understood. (Pro)renin receptor (PRR) functions as an accessory protein to a V-ATP-ase responsible for acidic pH maintenance in intracellular compartments, and recent data indicate that PRR could be a regulator of Wnt signaling. A circulating fragment (sPRR) is generated by enzymatic cleavage of the extracellular domain and can be quantified in plasma, serum and urine. Objectives. This is a pilot study, to explore the serum concentrations of the soluble (pro)renin receptor (sPRR) in patients with systemic sclerosis (SSc). Patients and methods. Serum samples from 29 subjects with a confirmed diagnosis of SSc have been tested using an ELISA method. Clinical and laboratory parameters have been analysed for associations with sPRR serum levels. Results and conclusion. Serum levels of sPRR were higher in patients with a history of digital ulcers (p 0.041, Mann-Whitney U-test) and those with digital pitting scars (p 0.037, Mann-Whitney U-test). Serum levels of sPRR correlated with serum creatinine (r 0.424, Spearman test), in line with previously reported data. Our results indicate the need for a larger study to assess the sPRR changes in patients with SSc, including more cases with severe disease and excluding a possible impact of angiotensin-receptor blockers.

scholarly journals Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

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 ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Vascular Involvement ◽  
Digital Ulcers ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Pbmc Culture ◽  
Significant Difference ◽  
Skin Biopsies

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.

scholarly journals Endothelin-1 Levels in Scleroderma Patients: A Pilot Study

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Emanuele Cozzani ◽  
Sanja Javor ◽  
Erika Laborai ◽  
Massimo Drosera ◽  
Aurora Parodi
Keyword(s):  
Retrospective Study ◽  
Systemic Sclerosis ◽  
Pilot Study ◽  
Serum Levels ◽  
Vascular Wall ◽  
Digital Ulcers ◽  
Normal Range ◽  
Endothelin 1 ◽  
Treatment And Prevention ◽  
Severity Of The Disease

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, which mediates vascular wall cells proliferation, fibrosis, and inflammation through two types of ET-1 receptors (ET-A and ET-B). In our retrospective study the serum levels of ET-1 in 18 systemic sclerosis (SSc) patients with and without digital ulcers (DUs) were assessed to observe possible correlation between the levels of ET-1, the evolution of SSc, and the therapy with an ET-1 antagonist (bosentan). In all our patients, the levels of ET-1 were found higher than normal range and correlate with the severity of the disease. Furthermore we also observed that in patients without DUs the levels of ET-1 were higher and did not correlate with new DUs development. In conclusion, the levels of ET-1 in our studied patients do not correlate with the possible development of DUs. The reduction of ET-1 levels in DUs patients in therapy with bosentan confirms the efficacy of this molecule both for treatment and prevention of digital ulcers. The inhibition of ET-A receptor by its antagonist may activate the opposite ET-B receptors, with well-known function ET-1 degradation and reducing of ET-1 serum level as confirmed in our pilot study.

scholarly journals Effect of sildenafil on digital ulcers in systemic sclerosis: analysis from a single centre pilot study

2009 ◽  
Vol 69 (8) ◽  
pp. 1475-1478 ◽  
Author(s):  
C. S. Brueckner ◽  
M. O. Becker ◽  
T. Kroencke ◽  
D. Huscher ◽  
H. U. Scherer ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pilot Study ◽  
Digital Ulcers ◽  
Single Centre

801 EXOSOMES CONTAINING LUNG SELF-ANTIGENS COLLAGEN-V AND Kα1-TUBULIN ARE PREVALENT IN PATIENTS WITH SYMPTOMATIC GASTROESOPHAGEAL REFLUX: RESULTS FROM A PILOT STUDY

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Deepika Razia ◽  
Ranjithkumar Ravichandran ◽  
Sandhya Bansal ◽  
Sarah Fournier ◽  
Komeil Baboli ◽  
...  
Keyword(s):  
Pilot Study ◽  
Gastroesophageal Reflux ◽  
Lung Injury ◽  
Lung Transplant ◽  
Fold Increase ◽  
Serum Levels ◽  
Serum Samples ◽  
Humoral Factors ◽  
Transplant Patients ◽  
Self Antigens

Abstract   Gastroesophageal reflux disease (GERD) has been associated with aspiration-induced pulmonary injury; however, good clinical or laboratory markers are not available. Increased serum levels of exosomes containing normally sequestered primary lung self-antigens (collagen-V, Kα1-tubulin) have been associated with lung injury in the lung transplant population. The aim of this pilot study was to assess the prevalence of exosomes containing collagen-V and/or Kα1-tubulin in patients with severe GERD. Methods After IRB approval, the institutional biobank database was queried to identify non-lung transplant patients who underwent primary anti-reflux surgery (ARS) from 2019 to 2020. Serum samples were retrieved from the repository. Exosome pellets were isolated using the Invitrogen® kit using the manufacturer’s protocol. The size of exosomes in the pellet was confirmed using NanoSight. Western blot of the exosomes was used to isolate and quantify collagen-V and Kα1-tubulin, using CD-9 as the standard. A ratio &gt; 1 was considered abnormal. Results Ten patients (6 females) with a median (IQR) age of 53 (42, 63) years were included in this study. All patients had symptomatic GERD as an indication for ARS. Five patients (50%) had exosomes containing abnormal levels of collagen-V and/or Kα1-tubulin (Figure 1). There was a mean 2.9- and 8.2-fold increase in collagen-V and Kα1-tubulin, respectively. Conclusion Humoral factors associated with lung injury are highly prevalent in patients undergoing elective ARS for GERD. This suggests that detection of exosomes containing lung self-antigens collagen-V and Kα1-tubulin could be useful as a biomarker of GERD-induced lung injury.

Serum Levels of Galectin-3: Possible Association with Fibrosis, Aberrant Angiogenesis, and Immune Activation in Patients with Systemic Sclerosis

2012 ◽  
Vol 39 (3) ◽  
pp. 539-544 ◽  
Author(s):  
TAKASHI TANIGUCHI ◽  
YOSHIHIDE ASANO ◽  
KANAME AKAMATA ◽  
SHINJI NODA ◽  
YURI MASUI ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Immune Activation ◽  
Developmental Process ◽  
Systolic Pressure ◽  
Serum Levels ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
Ventricular Systolic Pressure ◽  
Multifunctional Protein ◽  
Galectin 3

Objective.Galectin-3 is a multifunctional protein implicated in a variety of biological processes including fibrosis, angiogenesis, and immune activation, all of which are associated with the development of systemic sclerosis (SSc). We investigated the clinical significance of serum galectin-3 levels in SSc.Methods.Serum galectin-3 levels were determined by a specific ELISA in 58 patients with SSc and 19 healthy controls.Results.Serum galectin-3 levels were significantly lower in patients with diffuse cutaneous SSc (dcSSc) than in controls (3.29 ± 3.27 ng/ml vs 4.91 ± 2.67 ng/ml, respectively; p < 0.05), while being comparable between limited cutaneous SSc (3.70 ± 2.39 ng/ml) and healthy controls. In dcSSc, serum galectin-3 levels significantly correlated with total skin score (r = 0.45, p < 0.05). Serum galectin-3 levels were significantly decreased in early dcSSc (disease duration < 1 year; 1.64 ± 1.74 ng/ml; p < 0.05), but not in mid-stage dcSSc (1 to 6 years; 3.22 ± 3.16 ng/ml) or late-stage dcSSc (> 6 years; 4.86 ± 4.10 ng/ml), compared with controls. Serum galectin-3 levels were higher in SSc patients with both digital ulcers (DU) and elevated right ventricular systolic pressure (RVSP) than in those without each symptom (DU: 5.44 ± 3.74 ng/ml vs 2.99 ± 2.36 ng/ml, p < 0.05; elevated RVSP: 4.44 ± 3.14 ng/ml vs 2.82 ± 2.64 ng/ml, p < 0.05).Conclusion.Galectin-3 may be related to the developmental process of skin sclerosis in dcSSc and of DU and pulmonary vascular involvements in total SSc.

Upregulation of Myxovirus-resistance Protein A: A Possible Marker of Type I Interferon Induction in Systemic Sclerosis

2008 ◽  
Vol 35 (11) ◽  
pp. 2192-2200 ◽  
Author(s):  
PAOLO AIRÒ ◽  
CLAUDIA GHIDINI ◽  
CINZIA ZANOTTI ◽  
MIRKO SCARSI ◽  
ROBERTO CATTANEO ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Type I Interferon ◽  
Severe Disease ◽  
Protein A ◽  
Digital Ulcers ◽  
Type I ◽  
Healthy Controls ◽  
Type I Ifn ◽  
Resistance Protein ◽  
Reliable Marker

ObjectiveTo examine whether myxovirus-resistance protein A (MxA) mRNA expression, commonly considered a reliable marker of Type I interferon (IFN) bioactivity, is modified in patients with systemic sclerosis (SSc); if it is associated to specific clinical features; and if its modulation is accompanied by modulation of mRNA for the Type I IFN receptor (IFNAR).MethodsQuantification of mRNA for MxA and the subunit IFNAR1 and isoforms of IFNAR2 was performed by real-time polymerase chain reaction in 50 patients with SSc. Results were compared with those obtained from healthy controls and patients with another autoimmune disease such as multiple sclerosis.ResultsLevels of MxA mRNA above the 99th percentile of values found in healthy controls were observed in 9 out of 50 patients with SSc (p < 0.001). Induced MxA expression was significantly associated with some features of more severe disease, such as lower forced vital capacity and the presence of ischemic digital ulcers. No differences in the levels of IFNAR were found within MxA-induced and MxA-non-induced patients, but there was a direct correlation between levels of MxA and the soluble isoform of IFNAR2.ConclusionOur results show induction of MxA expression in some patients with SSc, which correlates with the presence of ischemic ulcers and other signs of worse disease, suggesting a potential role of Type I IFN in the pathogenesis of this disease and/or its complications.

Involvement of functional autoantibodies against vascular receptors in systemic sclerosis

2010 ◽  
Vol 70 (3) ◽  
pp. 530-536 ◽  
Author(s):  
Gabriela Riemekasten ◽  
Aurélie Philippe ◽  
Melanie Näther ◽  
Torsten Slowinski ◽  
Dominik N Müller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Transforming Growth Factor ◽  
Solid Phase ◽  
Biological Effects ◽  
Severe Disease ◽  
Study Cohort ◽  
Serum Samples ◽  
Related Mortality

BackgroundSystemic sclerosis (SSc) features autoimmunity, vasculopathy and tissue fibrosis. The renin-angiotensin and endothelin systems have been implicated in vasculopathy and fibrosis. A role for autoantibody-mediated receptor stimulation is hypothesised, linking three major pathophysiological features consistent with SSc.MethodsSerum samples from 478 patients with SSc (298 in the study cohort and 180 from two further independent cohorts), 372 healthy subjects and 311 control-disease subjects were tested for antibodies against angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) by solid phase assay. Binding specificities were tested by immunoprecipitation. The biological effects of autoantibodies in microvascular endothelial cells in vitro were also determined, as well as the quantitative differences in autoantibody levels on specific organ involvements and their predictive value for SSc-related mortality.ResultsAnti-AT1R and anti-ETAR autoantibodies were detected in most patients with SSc. Autoantibodies specifically bound to respective receptors on endothelial cells. Higher levels of both autoantibodies were associated with more severe disease manifestations and predicted SSc-related mortality. Both autoantibodies exert biological effects as they induced extracellular signal-regulated kinase 1/2 phosphorylation and increased transforming growth factor β gene expression in endothelial cells which could be blocked with specific receptor antagonists.ConclusionsFunctional autoimmunity directed at AT1R and ETAR is common in patients with SSc. AT1R and ETAR autoantibodies could contribute to disease pathogenesis and may serve as biomarkers for risk assessment of disease progression.

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