scholarly journals Evaluation of caspase 1 and sFas serum levels in patients with systemic sclerosis: correlation with lung dysfunction, joint and bone involvement

2003 ◽  
Vol 12 (6) ◽  
pp. 339-343
Author(s):  
Bozena Dziankowska-bartkowiak ◽  
Elzbieta Waszczykowska ◽  
Anna Zalewska ◽  
Anna Sysa-jedrzejowska

Recent studies point out at the role of apoptosis disturbances in the development of systemic sclerosis (SSc).The aim of our study was to examine caspase 1 and sFas serum levels in scleroderma patients and correlate the obtained results with skin involvement and internal organ changes.We studied 29 patients (14 with limited and 15 with diffuse SSc). The extension of skin involvement was measured using Total Skin Score (TSS). Internal organ involvement was assessed by specialist procedures. Serum caspase 1 and sFas levels were measured by enzyme-linked immunosorbent assay.We found correlation between sFas serum level and duration of Raynaud's phenomenon and TSS; caspase 1 serum level correlated only with TSS. Correlations between caspase 1 and lung dysfunction and sFas levels with joint and bone involvement in SSc patients were also observed.The obtained results revealed that disturbances of apoptosis might play a role in SSc pathogenesis. Caspase 1 and sFas serum levels correlate with the skin involvement severity, lung dysfunction, joint and bone changes.

2019 ◽  
Vol 312 (6) ◽  
pp. 453-458
Author(s):  
Anna Stochmal ◽  
Joanna Czuwara ◽  
Michał Zaremba ◽  
Lidia Rudnicka

Abstract Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by progressive fibrosis, vascular impairment and immune abnormalities. In recent years, adipokines (mediators synthetized by adipose tissue) have been indicated as a possible missing link in the pathogenesis of SSc. The aim of this study was to investigate the serum concentration of metabolic adipose tissue factors: adiponectin, resistin, leptin and endothelial proteins: endothelin-1, fractalkine and galectin-3 in patients with systemic sclerosis. The study included 100 patients with confirmed SSc diagnosis and 20 healthy individuals. The concentration of respective proteins was determined by enzyme-linked immunosorbent assay. The following markers showed statistically significant increased mean concentrations in patients with SSc in comparison to healthy control: resistin (13.41 vs 8.54 ng/mL; P = 0.0012), endothelin-1 (1.99 vs 1.31 pg/mL; P = 0.0072) and fractalkine (2.93 vs 1.68 ng/mL; P = 0.0007). Elevated serum levels of galectin-3 (4.54 vs 3.26 ng/mL; P = 0.0672) and leptin (19,542 vs 14,210 pg/mL; P = 0.1817) were observed. Decreased concentration of adiponectin was found in patients with SSc (5150 vs 8847 pg/mL; P = 0.0001). Fractalkine and galectin-3 levels were significantly higher in diffuse cutaneous SSc than limited cutaneous SSc subset (3.93 ng/mL vs 2.58 ng/mL, P = 0.0018; 6.86 ng/mL vs 3.78 ng/mL, P = 0.0008, respectively) and correlated positively with modified Rodnan Skin Score in total SSc patients (r = 0.376, P = 0.0009; r = 0.236, P = 0.018, respectively). In conclusion, an increased serum level of resistin associated with increased endothelin-1 and fractalkine level and decreased adiponectin level may indicate a significant role of the adipose tissue in the development and progression of vascular abnormalities in patients with systemic sclerosis. Fractalkine and galectin-3 may participate in promoting and exacerbating the fibrotic process in SSc.


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 ◽  
Author(s):  
Yuto Tamura ◽  
Tamihiro Kawakami ◽  
Yupeng Dong ◽  
Miku Yoshinari ◽  
Yuka Nishibata ◽  
...  

Abstract Objective. It was previously demonstrated that cutaneous vasculitis, including IgA vasculitis and cutaneous arteritis (CA), is associated with the presence of IgM antibodies (Abs) against the phosphatidylserine/prothrombin complex (PS/PT). Recently, novel enzyme-linked immunosorbent assay kits for the detection of IgG and IgM anti-PS/PT (aPS/PT) Abs have become commercially available.Methods. The prevalence of serum IgG and IgM aPS/PT Abs in both cutaneous and systemic vasculitis was determined using these kits. In addition, to examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild-type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell-free histones (250 µg/ml, 300 µl/site) 2 hours in advance. Results. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and CA compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild-type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming—subcutaneous histone injection—developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. Conclusion. IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis.


2020 ◽  
Author(s):  
Ramin Lotfi ◽  
Mohsen Molaie ◽  
Ehsan Mohammadi Noori ◽  
Khalil Soleiman ◽  
Amir Kiani

Adipose tissue-derived hormones known as adipokines, like leptin, have multiple bioactions. Notwithstanding the key roles of leptin in regulating energy homeostasis and metabolism, its cardiovascular functions are complex and not fully understood. This study aimed to investigate the association between serum concentrations of leptin and lipid profiles in patients with valve calcification. Seventy-two patients with valve calcification and 72 healthy individuals participated in this case-control study. The serum levels of biochemical markers and leptin were measured by the standard enzymatic methods and enzyme-linked immunosorbent assay (ELISA) technique, respectively. Significantly increased serum concentrations of FBS (P=0.001), urea (P<0.0001), creatinine (P=0.018), P (P<0.0001), LDL-C (P=0.011) and lower Ca (P=0.006), and HDL-C (P<0.0001) levels were observed in patients compared to controls. There was no significant difference in the serum level of TG and TC of patients than controls. Systolic and diastolic blood pressures were significantly increased in patients relative to controls (P<0.0001). However, a significantly diminished serum level of leptin was observed in patients than controls (P<0.0001). The correlation analysis demonstrated that the serum leptin concentration is negatively correlated with creatinine, but it is positively correlated with systolic blood pressure (P=0.0302, P=0.0362, respectively). There was no statistically significant association between serum levels of leptin and lipid profiles. Our findings indicated dyslipidemia and reduced serum leptin concentrations in patients with valve calcification, suggesting the role of lipid abnormalities and reduced leptin levels in the development and pathogenesis of valve calcification diseases.


Author(s):  
Т.Н. Жевак ◽  
Н.П. Чеснокова ◽  
Т.В. Шелехова ◽  
О.Е. Царева ◽  
И.А. Будник ◽  
...  

Цель. Изучить закономерности изменения экспрессии интерлейкина-10 и интерлейкина-24, обладающих иммуномодулирующим эффектом, при развитии B-клеточного хронического лимфолейкоза. С учетом этого выявить информативные прогностические критерии развития гемобластоза и/или нового подхода к терапии заболевания. Методы. У 120 больных с разными стадиями В-клеточного хронического лимфолейкоза методом твердофазного иммуноферментного анализа исследована динамика уровней интерлейкина-10 и интерлейкина-24 в сыворотке крови. Результаты. Обнаружено закономерное повышение содержания интерлейкина-10 и интерлейкина-24 в сыворотке крови пациентов уже на начальной стадии B-клеточного хронического лимфолейкоза и сохранение их достоверно высоких уровней на последующих стадиях заболевания. Заключение. Обнаруженный нами факт повышения содержания интерлейкина-10 в сыворотке крови пациентов с В-клеточным хроническим лимфолейкозом является фактором риска снижения противоопухолевой защиты организма вследствие подавления им механизмов клеточного иммунитета и способности ингибировать апоптоз малигнизированных клеток. Напротив, повышение экспрессии интерлейкина-24, обладающего проапоптотической активностью и стимулирующего дифференцировку клеток, может способствовать повышению эффективности механизмов противоопухолевой резистентности организма. Устранение дисбаланса продукции и/или содержания указанных цитокинов в сыворотке крови может создать условия повышения эффективности терапии пациентов с В-клеточным хроническим лимфолейкозом. Aim. To study serum levels of immunosuppressive cytokines (interleukin (IL)-10 and IL-24) in patients with B-cell chronic lymphocytic leukemia for assessment of the disease progression and elaboration of a new treatment strategy. Methods. 120 patients with B-cell chronic lymphocytic leukemia were enrolled in the study and divided into four groups according to the disease stage (Rai stage I-IV). Control group included 30 healthy volunteers. Concentrations of IL-10 and IL-24 were measured in serum using the enzyme-linked immunosorbent assay (ELISA). Results. Serum levels of IL-10 and IL-24 levels were significantly increased in all patient groups compared to the control. No difference in the cytokines levels between the patient groups was observed. Conclusion. In patients with B-cell chronic lymphocytic leukemia, the increased serum level of IL-10 might impair the antitumor defence by inhibiting the cell immune response and preventing apoptosis of malignant lymphocytes. On the other hand, the increased serum level of IL-24 might oppose these effects by promoting cellular differentiation and inducing apoptosis in malignant cells. Therefore, correction of IL-10/IL-24 imbalance may be a beneficial therapeutic strategy for patients with B-cell chronic lymphocytic leukemia.


2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Drahomira Holmannova ◽  
Lenka Borska ◽  
Ctirad Andrys ◽  
Pavel Borsky ◽  
Jan Kremlacek ◽  
...  

Background. Psoriasis is a chronic systemic inflammatory disease associated with a wide range of comorbidities, including metabolic syndrome (MetS). Serum calprotectin, ANGPTL8, and oxidative damage to nucleic acids might be associated with both diseases. The presented study describes the influence of psoriasis and MetS on the serum levels of markers of systemic inflammation (calprotectin and ANGPTL8) and markers of oxidative damage to nucleic acids. The applicability of serum levels of calprotectin and ANGPTL8 for monitoring of the activity of psoriasis (diagnostic markers) is also evaluated. Methods. Clinical examination (PASI score, MetS), enzyme-linked immunosorbent assay (ELISA), and Enzyme Immunoassay (EIA). Serum calprotectin, ANGPTL8, 8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine. Results and Conclusions. The psoriasis significantly increased the serum level of calprotectin and the serum level of oxidative damage to nucleic acids, however not the serum level of ANGPTL8. The presence of MetS did not significantly affect the serum levels of calprotectin, ANGPTL8, and oxidative damage to nucleic acids in either psoriasis patients or controls. It seems that the serum level of calprotectin (but not the serum level of ANGPTL8) could be used as a biomarker for monitoring the activity of psoriasis.


2020 ◽  
Author(s):  
Julien Guiot ◽  
Makon-Sébastien Njock ◽  
Béatrice André ◽  
Fanny Gester ◽  
Monique Henket ◽  
...  

Abstract Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-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.Methods: 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. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts. Results: Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r=0.6, p<0.001). Receiver operating characteristic curve analysis enabled us to identify that baseline IGFBP-2<105 ng/ml was associated with a better outcome (low risk to display KCO<70% predicted) at 2-year follow-up (area under the curve=0.75 at 75% sensibility and 68% specificity, p<0.05). In vitro functional study showed that IGFBP-2 significantly reduced fibroblast proliferation and pro-fibrotic activity.Conclusions: We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 698.1-698
Author(s):  
C. Chen ◽  
S. Yang ◽  
Z. Jiang ◽  
W. Wan ◽  
H. Zou ◽  
...  

Background:Serum fibrotic markers for systemic sclerosis (SSc) remain limited. The Enhanced Liver Fibrosis (ELF) score, originally derived and validated in patients with chronic liver disease, is an algorithm combining 3 serum markers, known as procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1), and hyaluronic acid (HA). The combined score was proved to be superior to the single components in reflecting the severity of liver fibrosis. However, the performance of ELF score and its components has not been fully validated in SSc.Objectives:To investigate PIIINP, TIMP-1, HA, and the combined algorithm ELF score as fibrotic markers for SSc skin involvement.Methods:Eighty SSc patients (44 dcSSc and 36 lcSSc), fulfilling the 2013 ACR/EULAR criteria with the absence of chronic liver diseases, were enrolled. Eighty age- and sex- matched healthy controls were also included. Serum PIIINP and HA levels were quantified by chemiluminescence immunoassay. Serum TIMP-1 levels were determined by enzyme-linked immunosorbent assay. The ELF score was calculated using the formula ELF score= 2.494 + 0.846*ln(HA) + 0.735*ln(PIIINP) + 0.391*ln(TIMP-1). Results were correlated with clinical profiles including modified Rodnan skin score (mRSS) and interstitial lung disease (ILD).Results:Compared with healthy controls, patients with SSc showed significantly elevated serum PIIINP (11.2±4.8 vs. 5.73±1.4μg/L, p<0.001), TIMP-I (123.7±78.6 vs. 67.8±26.5 ng/ml, p<0.001), and ELF score (10.5±0.9 vs. 9.7±0.4, P<0.001). Even higher levels of PIIINP, TIMP-1, and ELF score were observed in dcSSc patients, compared with lcSSc patients (p<0.001, p=0.024, p=0.003, respectively). No significant difference was found in the levels of serum HA between patients and controls. Strong correlations were observed between mRSS and ELF score (r=0.54, p<0.001), and between mRSS and PIIINP(r=0.62, p<0.001), whereas only weak correlations could be observed between mRSS and TIMP-1 (r=0.28, p=0.02), and between mRSS and HA (r=0.26, p=0.03). When stratified by ELF score, using cutoffs proposed for liver fibrosis and cirrhosis, SSc patients with ELF<9.8 showed the lowest mRSS on average, while patients with ELF>11.3 showed the highest (p<0.001). When stratified by serum PIIINP levels, using the 25th and 75th percentiles, SSc patients with serum PIIIINP levels<7.8μg/L showed the lowest mRSS on average, while patients with PIIINP>14.0μg/L showed the highest (p<0.001). Neither the ELF score nor its components showed significant difference between patients with and without ILD.Conclusion:The ELF score could be used for reflecting the severity of overall skin involvement in SSc, and serum PIIINP also increased in parallel with the increase of mRSS. Longitudinal prospective studies exploring ELF score or serum PIIINP as fibrotic markers and outcome measures of SSc are warranted.References:[1]Lichtinghagen R, Pietsch D, Bantel H, et al. The Enhanced Liver Fibrosis (ELF) score: Normal values, influence factors and proposed cut-off values. Journal of Hepatology. 2013; 59: 236-42.[2]Abignano G, Blagojevic J, Bissell LA, et al. European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis. Rheumatology. 2019; 58: 254-59.Figure 1.Correlations of mRSS with ELF score (A) and serum PIIINP (B) and distribution of mRSS among different ELF (C) and PIIINP (D) ranges.Acknowledgements:The authors have no acknowledgements to declare.Disclosure of Interests:None declared


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2059-2059
Author(s):  
O. L. Chinot ◽  
F. Boudouresque ◽  
C. Bequet ◽  
M. Barrie ◽  
A. Thiebaut ◽  
...  

2059 Background: Identification of circulating markers that predict tumor response or reflect progression is of crucial importance when using antiangiogenic agents. However, to date, no such parameters have been identified particularly for bevacizumab, for which, recently, increasing data have supported a role in patient with recurrent malignant glioma. Methods: Serial serum levels of VEGF, VEGFR2, FGF, SDFα, urokinase plasminogen activator (uPA), plasminogen activator inhibitor type I (PAI-1), and metalloprotesase type 9 (MMP9) were determined in a cohort of 32 patients treated with bevacizumab and irinotecan for recurrent malignant glioma. Samples were collected at the start of treatment and then at 4 weeks intervals until progression. Serum levels were measured using an enzyme-linked immunosorbent assay. Progression was defined by MacDonald's criteria, modified by integrating increase of infiltration as measured on MRI by Flair sequence. All subjects were followed for PFS and OS. Cox model analysis is used for correlation between markers and clinical outcome. Results: This preliminary analysis is restricted to pre-treatment (D0; n = 32), day 30 (D30; n = 27), and at progression time (DP; n = 15). None of the pretreatment serum level (n = 32) significantly affect PFS or OS although uPA and MMP9 tend to influence OS. Decrease of median level of all serum markers except PAI1 and VEGFR2 is observed from D0 to D30 under bevacizumab therapy, but only uPA and FGF variations tend to impact clinical outcome. From D30 to DP, increase of uPA is correlated to PFS (p = 0.028) while the observed increased of FGF and SDFα fail to reach significant correlation to PFS and OS. Conclusions: Increase of uPA serum level appear to be correlated to disease progression for patients with recurrent malignant glioma treated with bevacizumab and may reflect the invasive phenotype of glioma progression. Serum uPA may help in assessing treatment response under bevacizumab and warrant further studies. No significant financial relationships to disclose.


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