scholarly journals The role of klotho in systemic sclerosis

Reumatismo ◽  
2017 ◽  
Vol 69 (4) ◽  
pp. 156 ◽  
Author(s):  
R. Talotta ◽  
S. Bongiovanni ◽  
T. Letizia ◽  
F. Rigamonti ◽  
F. Atzeni ◽  
...  

The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc), through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan’s Skin Score, Medsger’s scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8) years) and 77 healthy controls (28 females, mean age 49.7±10.2 years). In the group of SSc patients, 19 (27.5%) suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine). The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001). However, Spearman’s test showed no significant association between klotho serum levels and disease activity, concerning either clinical, laboratory or instrumental findings. Our data show a significant deficit of klotho in SSc patients although any significant association was detected between klotho serum concentration and the clinical, laboratory or instrumental features of the disease. However, due to the limits of the study, further investigations are required.

Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Fabio Massimo Perrotta ◽  
Fulvia Ceccarelli ◽  
Cristiana Barbati ◽  
Tania Colasanti ◽  
Antonia De Socio ◽  
...  

Objective. Several molecules are involved in the pathogenesis of a new bone formation in ankylosing spondylitis (AS). The aim of this study was to evaluate the serum levels of sclerostin in patients with AS as a possible biomarker and to investigate any correlations with radiographic damage, disease activity, and function. Methods. AS patients fulfilled the modified New York criteria, and healthy controls were enrolled for this study. BASDAI, ASDAS-CRP, BASMI, BASFI, patient and physician VAS, and C-reactive protein were evaluated at baseline visit. Spinal damage was assessed using the mSASSS on radiographs performed within 3 months from baseline. Serum concentrations of sclerostin were assessed at baseline and after four months of therapy in patients who started an anti-TNF. Results. Twenty healthy subjects and 40 AS patients were enrolled in the study. In our group, serum sclerostin levels (median (25th–75th percentile)) were significantly higher in healthy controls (18.04 (13.6–24) pg/ml) than in AS patients (6.46 (4.5–11.1) pg/ml; P value < 0.01). However, no significant correlations were found between serum sclerostin levels and radiographic damage, assessed by mSASSS, and between serum sclerostin levels and clinical indices of activity and disability or with laboratory parameters. Sclerostin levels did not show significant changes after 4 months of anti-TNF therapy. Conclusions. The results of our study suggest a possible role of sclerostin in the identification of AS patients. Further studies are needed to prove the role of sclerostin as a disease activity biomarker and progression of disease in AS.


2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Victoria Furer ◽  
Eyal Hazan ◽  
Adi Mor ◽  
Michal Segal ◽  
Avi Katav ◽  
...  

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. Methods. 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. Results. The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), p=0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. Conclusion. Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS.


2020 ◽  
pp. 1-8
Author(s):  
Maryam Zarrabi ◽  
Mohammadali Nazarinia ◽  
Abbas Rahimi Jaberi ◽  
Nasser Gholijani ◽  
Zahra Amirghofran

<b><i>Objective:</i></b> Interleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc). <b><i>Subjects and Methods:</i></b> A total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA. <b><i>Results:</i></b> Levels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, <i>p</i> &#x3c; 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, <i>p</i> = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (<i>p</i> = 0.007) and new/recently untreated SSc patients (<i>p</i> = 0.032) were significantly higher than those in healthy controls. <b><i>Conclusion:</i></b> The higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Rossella Talotta ◽  
Sara Bongiovanni ◽  
Teresa Letizia ◽  
Federica Rigamonti ◽  
Maria Chiara Ditto ◽  
...  

Background. The aim of our study was to evaluate the serum concentration of klotho in a cohort of systemic sclerosis (SSc) patients compared to that of healthy controls and to correlate its levels with the degree and the kind of organ involvement. Methods. Blood samples obtained from both patients and controls were collected and analysed by an ELISA test for the determination of human soluble klotho. Scleroderma patients were evaluated for disease activity through clinical, laboratory, and instrumental assessment. Results. Our cohort consisted of 81 SSc patients (74 females, mean age 63.9 ± 13.1 years) and 136 healthy controls (78 females, mean age 50.5 ± 10.7 years). When matched for age, serum klotho concentration significantly differed between controls and patients (p<0.001). However, in SSc patients, we did not find any significant association between serum klotho and clinical, laboratory, and instrumental findings. Lower serum levels of klotho were detected in 4 patients who were anticitrullinated peptide antibody (ACPA) positive (p=0.005). Conclusions. Our data show a lower concentration of klotho in the serum of SSc patients compared to that of healthy controls, without any significant association with clinical manifestations and laboratory and instrumental findings. The association between serum klotho and ACPA positivity requires further investigation.


2009 ◽  
Vol 37 (2) ◽  
pp. 257-264 ◽  
Author(s):  
WOON PANG KUAN ◽  
LAI-SHAN TAM ◽  
CHUN-KWOK WONG ◽  
FANNY W.S. KO ◽  
TENA LI ◽  
...  

Objective.To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.Methods.Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.Results.The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).Conclusion.Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1382.2-1383
Author(s):  
J. E. Oller Rodriguez ◽  
E. Grau García ◽  
R. Gonzalez Mazario ◽  
M. De la Rubia Navarro ◽  
C. Pávez Perales ◽  
...  

Background:Systemic Sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement.It is mandatory to seek for biomarkers that help us with early diagnosis and that are also useful for predicting organic involvement, so that we can adjust the diagnostic and therapeutic approach.Objectives:Our aim was to check if the presence of CXCL4, CXCL8 and GDF-15 is greater in the disease than in healthy population, and also their involvement in organic damage.Methods:Observational and cross-sectional study, with a prospectively performed protocol, of patients diagnosed of SSc according to ACR/EULAR 2013 criteria. Demographic, clinical, analytical, activity (EUSTAR index), severity (Medsger scale and modified Rodnan index), health perception (SF36) and disability (HAQ and Cochin test) variables were collected. Moreover, Videocapillaroscopy (VCL) and Respiratory Function Test were made, as well High Resolution Lung Tomography and Echocardiography in order to describe pulmonary features. Serum levels of CXCL4, CXCL8 and GDF-15 were measured in SSc patients and in healthy controls.Results:A total of 42 patients (95.4% women) were included, with an average age of 59.2 years. The median of years since diagnosis was 4, by 6 since the first non-Raynaud symptom. 20 patients were diagnosed with limited SSc, 20 patients diffusely and 2 patients with SSc without scleroderma. 42 healthy controls were also included.We found significantly higher levels of GDF-15 in patients with SSc (P<0.001), without significant differences in CXCL4 and CXCL8 levels between patients with SSc and healthy controls.The presence of GDF-15 was associated with diffuse SSc (P=0.009), pulmonary arterial hypertension (P=0.038), interstitial lung disease (P=0.004), decreased forced vital capacity (FVC), (P=0.002), high serum titles of antiScl70 (P=0.006), increased disease activity measured by EUSTAR index (P=0.001), as with capillary dilations in Capillaroscopy (P=0.015).Moreover, we found an association between CXCL4 levels and the consumption of complement C3 fraction (P=0.008) and skin involvement (higher Rodnan modified score), (P = 0.001); not finding association with lung involvement or other features (spirometric or analytical changes, capillaroscopy or functional tests).Attending to CXCL8, it was associated to consumption of the C4 fraction of complement (P=0.013) and the presence of tortuosities in capillaroscopy (P=0.02) with no other significant findings.Conclusion:The presence of GDF-15 is associated with diffuse SSc, lung impairment, disease activity and changes in capillaroscopy. In addition, CXCL4 was only associated with skin involvement, while CXCL8 was not related to any organic damage in our patients.Disclosure of Interests:None declared


Dermatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Aleksandra Batycka-Baran ◽  
Wojciech Baran ◽  
Danuta Nowicka-Suszko ◽  
Maria Koziol-Gałczyńska ◽  
Andrzej Bieniek ◽  
...  

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. An important role of innate immune dysregulation in the pathogenesis of HS has been highlighted. S100A7 (psoriasin) is an innate, antimicrobial protein that exerts proinflammatory and chemotactic action. <b><i>Objectives:</i></b> The objective of the study was to investigate serum concentrations of S100A7 in individuals with HS as compared to healthy controls. Further, we evaluated the expression of S100A7 in lesional HS skin as compared to perilesional (clinically uninvolved) HS skin and normal skin. <b><i>Methods:</i></b> Serum concentrations of S100A7 were evaluated with a commercially available ELISA kit. The expression of S100A7 in the skin was assessed using qRT-PCR and immunofluorescence staining. <b><i>Results:</i></b> We found increased expression of S100A7 in lesional HS skin as compared to perilesional HS skin (<i>p</i> = 0.0017). The expression of S100A7 in lesional HS skin was positively associated with serum C-reactive protein concentration and the severity of disease according to Hurley staging. The serum concentration of S100A7 in individuals with HS was decreased as compared to healthy controls and patients with psoriasis. <b><i>Conclusions:</i></b> Upregulated in lesional HS skin, S100A7 may enhance the inflammatory process and contribute to the HS pathogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julien Guiot ◽  
Makon-Sébastien Njock ◽  
Béatrice André ◽  
Fanny Gester ◽  
Monique Henket ◽  
...  

AbstractSystemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. For this, we compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n = 102), among which SSc-no ILD (n = 63) and SSc-ILD (n = 39), compared to healthy subjects (HS) (n = 39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Serum level of IGFBP-2 was significantly increased in SSc patients compared to HS, and negatively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) (r = − 0.29, p < 0.01). Two-year longitudinal analysis in a subgroup of 28 SSc patients determined that IGFBP-2 variation was positively correlated with KCO at 2-year follow-up (r = 0.6, p < 0.001). SSc patients with a lower variation of IGFBP-2 (less than 22%) presented significant deterioration of pulmonary function at 2-year follow-up (p < 0.01). ROC curve analysis enabled us to identify that baseline IGFBP-2 > 105 ng/ml was associated with a poor outcome (KCO < 70% predicted) at 2-year follow-up (AUC = 0.75, p < 0.05). We showed for the first time that serum levels of IGFBP-2 might be a prognostic factor of the development of SSc-ILD.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1093.1-1093
Author(s):  
G. Pellegrino ◽  
K. Stefanantoni ◽  
F. Facioni ◽  
C. Angelelli ◽  
A. Gigante ◽  
...  

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared


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