scholarly journals OP0244 28 NEW AUTOANTIBODIES AGAINST GPCR, GROWTH FACTORS AND GROWTH FACTOR RECEPTORS ARE ASSOCIATED WITH DISEASE MANIFESTATIONS IN SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 149.1-150
Author(s):  
K. Sterner ◽  
C. J. K. Fouodo ◽  
I. König ◽  
A. Künstner ◽  
H. Busch ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Growth Factors ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Roc Analysis ◽  
Morbidity And Mortality ◽  
Receptor Type ◽  
Organ Involvement ◽  
Complement Receptors ◽  
Highly Correlated

Background:The morbidity and mortality of systemic sclerosis (SSc) are largely determined by vascular and fibrotic pathologies. Levels of autoantibodies (ab) against G protein-coupled receptors (GPCR), growth factors (GF) and growth factor receptors (GFR) are altered in SSc compared to healthy controls (HC) 1. Thus, higher angiotensin II receptor type 1 - (AT1R) and endothelin receptor type A - (ETAR) ab levels are associated with severe disease and SSc-related mortality 2. CXC motiv chemokine receptor 3 - (CXCR3) and 4 - (CXCR4) ab have predictive value for deterioration of pulmonary fibrosis (PF) 3.Objectives:We used statistical methods to identify associations between disease manifestations and 28 new ab directed against GPCR, GF and GFR in SSc.Methods:Ab against the following targets were measured in sera from SSc patients (n = 177) and HC (n = 88): Adrenoceptors alpha-1 (ADRA1), alpha-2 (ADRA2), beta-1 (ADRB1), beta-2 (ADRB2); muscarinoceptors 1-5 (M1R - M5R); AT1R, ETAR, endothelin B receptor (ETBR); CXCR3, CXCR4; complement receptors 3a (C3aR) and 5a (C5aR); protease-activated receptors 1 (PAR1) and 2 (PAR2); vascular endothelial growth factor A (VEGFA) and its receptors 1 (VEGFR1) and 2 (VEGFR2), epithelial growth factor (EGF)/ - receptor (EGFR); hepatocyte growth factor (HGF)/ - receptor (HGFR), platelet-derived growth factor-AA (PDGFAA), placental growth factor (PlGF).The organ involvement (PF, cardiac involvement, PAH, gastrointestinal tract) and quantitative markers (modified Rodnan skin score, SSc activity score, pulmonary function, cardiac enzymes and echocardiography, routine laboratory, autoimmune diagnostics) as well as demographic data were recorded retrospectively at the time of sample collection. Statistical analysis was performed using the Mann-Whitney U test (MWU), Pearson correlations, ROC analysis, and age-adjusted logistic regression models.Results:In SSc 20 of 28 measured ab levels are significantly altered compared to HC. According to the Pearson correlation matrix, the ab-levels are highly correlated and build a network that differs between HC and SSc. Furthermore, altered network signatures are formed in the differentiated analysis of several disease manifestations of SSc such as SSc-subtype or PF. Based on ROC analysis, FGF-ab, ADRB1-ab and PlGF-ab are well suited to predict SSc (Figure 1).In addition, limited cutaneous SSc (lSSc) patients displayed lower levels of most ab than diffuse cutaneous SSc patients, whereas cardiac and pulmonary involvement are associated with higher ab levels. In the logistic regression lSSc is associated with lower levels of ab against M1R, M2R, C5aR, ETAR, AT1R, PAR1, EGFR. Higher levels for ab against M1R, M2R, ETBR, C5aR are associated with PF, higher levels of ab against complement receptors, adrenoreceptors and EGF with NT-proBNP elevation.Conclusion:The newly described antibodies against GPCR, GF and GFR are highly correlated. Associations with morbidity- and mortality-determining organ involvement indicate their possible functional relevance and novel pathophysiological mechanisms. As new biomarkers, some of the ab have prognostic value for SSc; for other manifestations, their value should be evaluated in further studies.References:[1]Cabral-Marques, O., Marques, A., Giil, L.M. et al. GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis. Nat Commun9, 5224 (2018). https://doi.org/10.1038/s41467-018-07598-9[2]Riemekasten G, Philippe A, Näther M, et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis Annals of the Rheumatic Diseases 2011;70:530-536.[3]Weigold, F., Günther, J., Pfeiffenberger, M. et al. Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis. Arthritis Res Ther 20, 52 (2018). https://doi.org/10.1186/s13075-018-1545-8Disclosure of Interests:Kristina Sterner: None declared, Césaire J. K. Fouodo: None declared, Inke König: None declared, Axel Künstner: None declared, Hauke Busch: None declared, Harald Heidecke Shareholder of: Owner of CellTrend, Anja Schumann: None declared, Antje Müller: None declared, Gabriela Riemekasten: None declared, Susanne Schinke Grant/research support from: UCB sponsors EULAR registration fees

Nailfold Capillaroscopy for Prediction of Novel Future Severe Organ Involvement in Systemic Sclerosis

2013 ◽  
Vol 40 (12) ◽  
pp. 2023-2028 ◽  
Author(s):  
Vanessa Smith ◽  
Valeria Riccieri ◽  
Carmen Pizzorni ◽  
Saskia Decuman ◽  
Ellen Deschepper ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Systemic Sclerosis ◽  
Logistic Regression Analysis ◽  
Multiple Logistic Regression Analysis ◽  
Organ Involvement ◽  
Normal Pattern ◽  
Organ Systems ◽  
Vasoactive Medication ◽  
Pattern Versus

Objective.Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma (systemic sclerosis; SSc) (“early,” “active,” and “late”) with novel future severe clinical involvement in 2 independent cohorts.Methods.Sixty-six consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline. Images were blindly assessed and classified into normal, early, active, or late NVC pattern. Clinical evaluation was performed for 9 organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart, and kidney) according to the Medsger disease severity scale (DSS) at baseline and in the future (18–24 months of followup). Severe clinical involvement was defined as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous NVC predictor variable) was performed.Results.The OR to develop novel future severe organ involvement was stronger according to more severe NVC patterns and similar in both cohorts. In simple logistic regression analysis the OR in the Belgian/Italian cohort was 2.16 (95% CI 1.19–4.47, p = 0.010)/2.33 (95% CI 1.36–4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern, and 10.14/12.63 for the late pattern versus the normal pattern. In multiple logistic regression analysis, adjusting for disease duration, subset, and vasoactive medication, the OR was 2.99 (95% CI 1.31–8.82, p = 0.007)/1.88 (95% CI 1.00–3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active pattern, and 26.69/6.66 for the late pattern versus the normal pattern.Conclusion.Capillaroscopy may be predictive of novel future severe organ involvement in SSc, as attested by 2 independent cohorts.

Insulin and epidermal growth factor are growth factors for isolated porcine thyroid follicles

1985 ◽  
Vol 110 (1_Suppla) ◽  
pp. S74
Author(s):  
R. GÄRTNER ◽  
W. GREIL ◽  
R. DEMHARTER ◽  
K. HORN
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epidermal Growth

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals Growth factors in the regulation of reparative response in the presence of peritoneal damage

2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Irina A. Shurygina ◽  
Мichael G. Shurygin ◽  
Lubov V. Rodionova ◽  
Nataliya I. Ayushinova
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Extended Period ◽  
Tissue Growth ◽  
Tissue Response ◽  
Heparin Binding ◽  
Lower Quadrant ◽  
Male Wistar Rats ◽  
The Right ◽  
Endothelial Growth Factor

AbstractObjectivesTo study the expression of growth factors in the regulation of tissue repair after peritoneal damage tissue response to peritoneal damage.MethodsExperimental study in 35 male Wistar rats determining the evolution over time of the tissue response to aseptic peritoneal damage. A standardized bowel and peritoneal lesions were created in the right lower quadrant by laparotomy. Then, tissular expression of growth factors was evaluated by multiplex polymerase chain reaction at seven timepoints between 6 h and 30 days, postoperatively.ResultsTissular responses of granulocyte-stimulating factors (Csf2, Csf3), connective tissue growth factor (Ctgf), epidermal growth factors and receptor (Egf, Egfr), fibroblast growth factors (Fgf2, 7 and 10), heparin binding EGF-like growth factor (Hbegf), hepatocyte growth factor (Hgf), insulin-like growth factor-1 (Igf1), mitogenic transforming growth factors (Tgfa, Tgfb1, Tgfbr3), and vascular endothelial growth factor A (Vegfa) were biphasic with a first expression peak at day 3, followed by a more pronounced peak at day 14.ConclusionsWe observed a long-lasting, widespread response of tissular growth factors for at least two weeks after peritoneal damage. To be clinically effective, the prophylaxis of postoperative adhesions might be needed for an extended period of time.

scholarly journals Utilizing the ABC Transporter for Growth Factor Production by fleQ Deletion Mutant of Pseudomonas fluorescens

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 679
Author(s):  
Benedict-Uy Fabia ◽  
Joshua Bingwa ◽  
Jiyeon Park ◽  
Nguyen-Mihn Hieu ◽  
Jung-Hoon Ahn
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Pseudomonas Fluorescens ◽  
Abc Transporter ◽  
Transforming Growth Factor Beta ◽  
Deletion Mutant ◽  
Transforming Growth Factor ◽  
Gene Knockout ◽  
Type I ◽  
Double Deletion

Pseudomonas fluorescens, a gram-negative bacterium, has been proven to be a capable protein manufacturing factory (PMF). Utilizing its ATP-binding cassette (ABC) transporter, a type I secretion system, P. fluorescens has successfully produced recombinant proteins. However, besides the target proteins, P. fluorescens also secretes unnecessary background proteins that complicate protein purification and other downstream processes. One of the background proteins produced in large amounts is FliC, a flagellin protein. In this study, the master regulator of flagella gene expression, fleQ, was deleted from P. fluorescens Δtp, a lipase and protease double-deletion mutant, via targeted gene knockout. FleQ directs flagella synthesis, so the new strain, P. fluorescens ΔfleQ, does not produce flagella-related proteins. This not only simplifies purification but also makes P. fluorescens ΔfleQ an eco-friendly expression host because it will not survive outside a controlled environment. Six recombinant growth factors, namely, insulin-like growth factors I and II, beta-nerve growth factor, fibroblast growth factor 1, transforming growth factor beta, and tumor necrosis factor beta, prepared using our supercharging method, were successfully secreted by P. fluorescens ΔfleQ. Our findings demonstrate the potential of P. fluorescens ΔfleQ, combined with our supercharging process, as a PMF.

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