scholarly journals HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

2019 ◽  
Vol 8 (1) ◽  
pp. 39
Author(s):  
Elisabetta Caselli ◽  
Irene Soffritti ◽  
Maria D’Accolti ◽  
Daria Bortolotti ◽  
Roberta Rizzo ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Plasma Levels ◽  
Human Herpesvirus ◽  
Infectious Agents ◽  
Internal Organs ◽  
Matrix Deposition ◽  
Skin Biopsies ◽  
Extracellular Matrix Deposition

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.

scholarly journals The Role of PPAR Gamma in Systemic Sclerosis

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Michelly Cristiny Pereira ◽  
Moacyr Jesus Barreto de Melo Rego ◽  
Laurindo Ferreira da Rocha ◽  
Ivan da Rocha Pitta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Fibrosis ◽  
Ppar Gamma ◽  
Immune Dysregulation ◽  
Unknown Etiology ◽  
Internal Organs ◽  
Medical Need

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγligands have been studiedin vitroandin vivoand some theories have emerged leading to new insights. Aberrant PPARγfunction seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγas an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.

scholarly journals Laminin α4 contributes to airway remodeling and inflammation in asthma

2019 ◽  
Vol 317 (6) ◽  
pp. L768-L777 ◽  
Author(s):  
Pavan Prabhala ◽  
David B. Wright ◽  
Patricia Robbe ◽  
Catrin Bitter ◽  
Tonio Pera ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Remodeling ◽  
Cell Phenotype ◽  
Asthmatic Patients ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Characteristic Features ◽  
Blocking Antibodies

Airway inflammation and remodeling are characteristic features of asthma, with both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the α2-chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma. The role of other laminin chains, including the laminin α4 and α5 chains, which contribute to leukocyte migration in other diseases, is currently unknown. The aim of the current study was to investigate the role of these laminin chains in ASM function and in AHR, remodeling, and inflammation in asthma. Expression of both laminin α4 and α5 was observed in the human and mouse ASM bundle. In vitro, laminin α4 was found to promote a pro-proliferative, pro-contractile, and pro-fibrotic ASM cell phenotype. In line with this, treatment with laminin α4 and α5 function-blocking antibodies reduced allergen-induced increases in ASM mass in a mouse model of allergen-induced asthma. Moreover, eosinophilic inflammation was reduced by the laminin α4 function-blocking antibody as well. Using airway biopsies from healthy subjects and asthmatic patients, we found inverse correlations between ASM α4-chain expression and lung function and AHR, whereas eosinophil numbers correlated positively with expression of laminin α4 in the ASM bundle. This study, for the first time, indicates a prominent role for laminin α4 in ASM function and in inflammation, AHR, and remodeling in asthma, whereas the role of laminin α5 is more subtle.

HLA-G Expression in the Skin of Patients with Systemic Sclerosis

2009 ◽  
Vol 36 (6) ◽  
pp. 1230-1234 ◽  
Author(s):  
ISABELA J. WASTOWSKI ◽  
PERCIVAL D. SAMPAIO-BARROS ◽  
ELIANE M.I. AMSTALDEN ◽  
GUSTAVO MARTELLI PALOMINO ◽  
JOÃO FRANCISCO MARQUES-NETO ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Control Sample ◽  
Healthy Controls ◽  
Skin Disorders ◽  
Disease Prognosis ◽  
Laboratory Variables ◽  
Skin Biopsies ◽  
Dermal Cells

Objective.To determine HLA-G expression in skin biopsies from patients with systemic sclerosis (SSc), and its association with epidemiological, clinical, and laboratory variables and survival.Methods.Paraffin-embedded skin biopsies obtained from 21 SSc patients (14 limited SSc, 7 diffuse SSc) and from 28 healthy controls were studied. HLA-G expression was evaluated by immunohistochemistry.Results.HLA-G molecules were detected in 57% of skin biopsies from patients with SSc (9 from limited SSc, 3 from diffuse SSc), whereas no control sample expressed HLA-G (p = 0.000004). In patients, HLA-G molecules were consistently observed within epidermal and some dermal cells. HLA-G expression was associated with a lower frequency of vascular cutaneous ulcers (p = 0.0004), telangiectasias (p = 0.008), and inflammatory polyarthralgia (p = 0.02). After a 15-year followup, SSc patients who exhibited HLA-G survived longer than patients who did not.Conclusion.HLA-G is expressed in skin biopsies from patients with SSc, and this is associated with a better disease prognosis. This suggests a modulatory role of HLA-G in SSc, as observed in other skin disorders.

scholarly journals Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2116
Author(s):  
Marija Geroldinger-Simić ◽  
Thomas Bögl ◽  
Markus Himmelsbach ◽  
Norbert Sepp ◽  
Wolfgang Buchberger
Keyword(s):  
Systemic Sclerosis ◽  
High Performance ◽  
Clinical Manifestations ◽  
Plasma Phospholipid ◽  
Phospholipid Metabolism ◽  
Internal Organs ◽  
New Biomarkers ◽  
First Time

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

scholarly journals TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amira Gabsi ◽  
Xavier Heim ◽  
Akram Dlala ◽  
Asma Gati ◽  
Haifa Sakhri ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Th17 Cells ◽  
Vascular System ◽  
Adaptive Immune Response ◽  
Autoimmune Disorder ◽  
Soluble Form ◽  
Adaptive Immune ◽  
Th17 Lymphocytes

AbstractSystemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of RORγT, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.

scholarly journals The role of beluntas (pluchea indica less.) leaf extract in preventing the occurrence of fibroblasts hyperproliferation: An in vitro preliminary study

2019 ◽  
Author(s):  
Sakti Charlia Maharani ◽  
Indah Julianto ◽  
Suci Widhiati
Keyword(s):  
Leaf Extract ◽  
In Vitro Study ◽  
Collagen I ◽  
Control Group ◽  
Antibody Treatment ◽  
Average Decrease ◽  
Matrix Deposition ◽  
Post Hoc

Beluntas (Pluchea indica Less.) is a herbal plant which contains variety of benefits. Quercetin, one of flavonoid, is the most bioactive agent in beluntas leaf. Collagen inhibition by quercetin may modulate extracellular matrix deposition and inhibit the formation of hypertrophic scar. This was an in vitro study with senescent fibroblasts to determine the role of beluntas leaf extract in preventing the occurence of fibroblasts hyperproliferations. There were 4 groups were stained by anti-collagen I antibodies and secondary antibody. Flowcytometry analysis was done to measure the fibroblasts density. Anova test was performed with a value of p=0.000 (p<0.05). A post hoc analysis showed significant differences in the average decrease of fibroblasts that absorbs staining anti-collagen I antibody treatment group compared with the control group. There were significant effects of beluntas leaf extract in preventing the occurrence of fibroblasts hyperproliferations. Beluntas leaf extract with a concentration of 80 mol/L had the most significant effect on the fibroblasts density. Thus beluntas leaf extract has the ability in preventing the occurrence of fibroblasts hyperproliferation.

scholarly journals Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy

Cell Reports ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 199-212.e5 ◽  
Author(s):  
Hirokazu Muraoka ◽  
Kazuhiro Hasegawa ◽  
Yusuke Sakamaki ◽  
Hitoshi Minakuchi ◽  
Takahisa Kawaguchi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Proximal Tubules ◽  
Renal Proximal Tubules ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition

scholarly journals Digital Ischemia in Scleroderma Spectrum of Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Elena Schiopu ◽  
Ann J. Impens ◽  
Kristine Phillips
Keyword(s):  
Extracellular Matrix ◽  
Systemic Sclerosis ◽  
Unknown Etiology ◽  
Digital Ulcers ◽  
Significant Morbidity ◽  
Matrix Deposition ◽  
Intimal Proliferation ◽  
Digital Ischemia ◽  
Autoimmune Processes ◽  
Extracellular Matrix Deposition

Systemic Sclerosis (Scleroderma, SSc) is a disease of unknown etiology characterized by widespread vasculopathy and extracellular matrix deposition leading to fibrosis and autoimmune processes. Digital ischemia (digital ulcers (DUs)) is the hallmark of SSc-related vasculopathy and is characterized by endothelial dysfunction leading to intimal proliferation and thrombosis. It happens frequently (30% of the patients each year) and it is associated with significant morbidity. This paper summarizes the current information regarding pathogenesis, definitions, management, and exploratory therapies in DUs associated with SSc.

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