scholarly journals Serum Calponin 3 Levels in Patients with Systemic Sclerosis: Possible Association with Skin Sclerosis and Arthralgia

2021 ◽  
Vol 10 (2) ◽  
pp. 280
Author(s):  
Hirohito Kotani ◽  
Ayumi Yoshizaki ◽  
Kazuki M. Matsuda ◽  
Yuta Norimatsu ◽  
Ai Kuzumi ◽  
...  

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis and vasculopathy in various organs with a background of inflammation initiated by autoimmune abnormalities. Calponin 3 plays a role in the cell motility and contractibility of fibroblasts during wound healing in the skin. We aimed to evaluate serum calponin 3 levels in SSc patients and their association with clinical manifestations of SSc. Serum samples were collected from 68 patients with SSc and 20 healthy controls. Serum calponin 3 levels were examined using enzyme-linked immunosorbent assay kits, and their association with clinical features of SSc was statistically analyzed. The upper limit of the 95% confidence interval of serum calponin 3 levels in healthy controls was utilized as the cut-off value when dividing SSc patients into the elevated and normal groups. Serum calponin 3 levels were significantly higher in SSc patients than in healthy controls (mean (95% confidence interval), 15.38 (14.66–16.11) vs. 13.56 (12.75–14.38) ng/mL, p < 0.05). The modified Rodnan total skin thickness score was significantly higher in the elevated serum calponin 3 level group than in the normal level group (median (25–75th percentiles), 10.0 (2.0–16.0) vs. 6.5 (3.25–8.75), p < 0.05). Moreover, SSc patients with increased serum calponin 3 levels also had a higher frequency of arthralgia (40% vs. 9%, p < 0.05). Elevated serum calponin 3 levels were associated with skin sclerosis and arthralgia in SSc patients. Serum calponin 3 levels might be a biomarker that reflects the severity of skin sclerosis and joint involvement in SSc.

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


2013 ◽  
Vol 5 (1) ◽  
pp. e2013044 ◽  
Author(s):  
Sameh Samir Fahmey ◽  
Hassan Naguib ◽  
Sanna Abdelshafy ◽  
Rasha Alashry

Background: The β-Thalassemia syndromes are the most common hereditary chronic hemolytic anemia due to impaired globin chain synthesis.  Vascular endothelial growth factor (VEGF) plays several roles in angiogenesis which is a crucial process in the pathogenesis of several inflammatory, autoimmune and malignant diseases .Endothelial damage and inflammation make a significant contribution to the pathophysiology of β-thalassemia. Purpose: The aim of the study was to assess serum VEGF level in children with beta-thalassemia major as a marker of angiogenesis. Methods: Blood samples were collected from 40 patients with thalassemia major and 10 healthy controls and assayed for VEGF by enzyme-linked immunosorbent assay. Results: VEGF level was significantly higher in patients with β-Thalassemia major than healthy controls (p=0.001).In addition, VEGF level was higher in splenectomised thalassemic patients than non splenectomised ones (p=0.001) .However, there were a positive correlation between VEGF and chelation starting age (p=0.008) and a negative correlation between VEGF and frequency of blood transfusion (p=0.002). Conclusion: thalassemia patients, especially splenectomized, have elevated serum levels of VEGF. Early chelation and regular blood transfusion help to decrease serum VEGF and the risk of angiogenesis.  


2015 ◽  
Vol 42 (3) ◽  
pp. 449-455 ◽  
Author(s):  
Yong Hou ◽  
Qing-li Zhu ◽  
He Liu ◽  
Yu-xin Jiang ◽  
Liang Wang ◽  
...  

Objective.To investigate skin elasticity using acoustic radiation force impulse (ARFI) quantification in systemic sclerosis (SSc), and compare the modified Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of the skin.Methods.Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age-matched and sex-matched healthy controls were evaluated. The SWV and thickness of skin were measured at 17 sites corresponding to those assessed in the mRSS in each participant. The SWV measurements of skin were compared between patients with dcSSc and healthy controls. The correlations between the mRSS and the skin SWV and thickness were explored using Spearman’s correlation.Results.The SWV values were higher in patients with dcSSc compared with healthy controls at right hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum, and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of uninvolved skin were higher than those of controls (p < 0.001), and the SWV values increased with increasing skin scores except for skin score 3 (p < 0.05). The sum of the SWV values correlated with total clinical skin score (r = 0.841, p < 0.001), and the sum of the skin thickness correlated with total clinical skin score (r = 0.740, p = 0.002).Conclusion.ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc. ARFI quantification could identify early skin change that may precede palpable skin involvement, and may be a valuable adjunct to skin evaluation in patients with SSc.


2009 ◽  
Vol 36 (9) ◽  
pp. 1917-1923 ◽  
Author(s):  
KOICHI YANABA ◽  
EIJI MUROI ◽  
AYUMI YOSHIZAKI ◽  
TOSHIHIDE HARA ◽  
FUMIHIDE OGAWA ◽  
...  

Objective.To determine serum concentrations of soluble CXCL16 and its clinical associations in patients with systemic sclerosis (SSc).Methods.Serum CXCL16 levels from 89 patients with SSc were examined by ELISA. In a retrospective longitudinal study, 68 sera from 28 patients with SSc were analyzed (followup 1.3 to 7.3 yrs).Results.Serum CXCL16 levels were elevated in patients with SSc compared with healthy controls (n = 42). Patients with diffuse cutaneous SSc (n = 52) had higher levels of CXCL16 than those with limited cutaneous SSc (n = 37). Serum CXCL16 levels correlated positively with the extent of skin sclerosis. In the longitudinal study, CXCL16 levels generally decreased on a parallel with the improvement in skin sclerosis.Conclusion.CXCL16 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis, suggesting that CXCL16 may have a role in the development of skin fibrosis in SSc. Blockade of CXCL16 interaction might be a potential therapeutic target in patients with SSc.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jie Shen ◽  
Zhangfang Li ◽  
Wenting Li ◽  
Ying Ge ◽  
Min Xie ◽  
...  

To determine serum cytokine profiles in Graves’ disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ(interferon-gamma), TNF-α(tumor necrosis factor-alpha), IL-1α(interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γand TNF-αwere elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lukas Bankamp ◽  
Beate Preuß ◽  
Ann-Christin Pecher ◽  
Nicola Beucke ◽  
Jörg Henes ◽  
...  

Objectives1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance.MethodsSera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients’ sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti–topo-I-abs.ResultsFifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation.ConclusionsFunctionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.


2020 ◽  
Vol 11 ◽  
pp. 204062232095642
Author(s):  
Mingxia Zhang ◽  
Liyun Zhang ◽  
Linning E ◽  
Ke Xu ◽  
Xu Fei Wang ◽  
...  

Background: Human epididymis protein 4 (HE4, also known as WFDC-2) has been implicated in fibrotic disorders pathobiology. We tested the hypothesis that HE4 may be used as a candidate biomarker for systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD). Methods: A total of 169 consecutive SSc patients and 169 age-and sex-matched healthy controls were enrolled and blood samples were collected. Pulmonary function tests (PFTs) and paired lavage was performed on 169 patients and 37 healthy controls. All patients were classified as having SSc-no ILD or SSc-ILD, based on high-resolution computed tomography (CT) scans of the chest, and a semiquantitative grade of ILD extent was evaluated through CT scans (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%). Serum and bronchoalveolar lavage fluid (BALF) HE4 levels were measured by enzyme-linked immunosorbent assay. Results: Serum HE4 levels were higher in SSc patients [median (interquartile range), 139.4 (85.9–181.8) pmol/l] compared with healthy controls [39.5 (24.3–54.2) pmol/l, p < 0.001] and were higher in patients with SSc-ILD [172.1 (94.8–263.3) pmol/l] than in those with SSc-no ILD [97.4 (85.5–156.5) pmol/l, p < 0.001]. This observation was replicated in the BALF samples. Corresponding values were 510.8 (144.6–1013.8) pmol/l for SSc cohort, 754.4 (299–1060) pmol/l for SSc-ILD, 555.1 (203.7–776.2) pmol/l for SSc-no ILD, and 238.7 (97.7–397.6) pmol/l for controls. The semiquantitative grade of ILD on CT scan was significantly proportional to the HE4 levels and the lung function parameter (i.e., FVC) had a negative correlation with the HE4 levels. Conclusion: This is the first study to demonstrate the potential clinical utility of blood and BALF HE4 as a biomarker for SSc-ILD. Future prospective validation studies are warranted.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sha-Sha Tao ◽  
Yi-Lin Dan ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
...  

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Naglaa Fathy Salama Sayed ◽  
Hoda Ahmed Mounib ◽  
Rania Mahmoud Elhusseiny

Abstract Background Systemic sclerosis and dermatomyositis are autoimmune connective tissue diseases affecting the skin and various internal organs. Systemic sclerosis is characterized by fibrotic arteriosclerosis of peripheral and visceral vasculature. Objective Analysis of video dermatoscopic picture of systemic sclerosis and dermatomyositis patients and find a characteristic feature for both. Assess serum vascular endothelial growth factor (VEGF) in these patients using enzyme linked immunosorbent assay (ELISA) kits. Perform a statistical analysis of the results to find a relation between video dermatoscopic Picture of systemic sclerosis and dermatomyositis patients and their serum VEGF to help in diagnosis, grading, prognosis and management. Patients and Methods Our case control study included 25 patients with SSc or DM (2555 years) recruited from Ain Shams University Hospitals and 25 apparent healthy controls with matched age and sex. After the study had been approved by Ain shams University of Medical Sciences Research Ethics Committee, all the subjects signed an informed consent before inclusion in the study. Results Serum VEGF level was highly significant in patients than in controls. This may be explained by the excessive release of VEGF in patients due to hypoxia caused by microvascular occlusion that not present in healthy controls. Conclusion Microvascular abnormalities are the earliest features of SSc and DM with elevation of serum VEGF level indicating its role in disease pathogenesis and disturbance of microvessls. Videodermoscopy and measurement of serum VEGF are effective tools in diagnosis, prognosis and grading of autoimmune connective tissue diseases as SSc and DM.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  

AbstractCD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. Although CD226 polymorphism is known to be involved in systemic lupus erythematosus (SLE), the involvement of soluble CD226 (sCD226) in SLE is still unknown. In the present study, we measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and the cumulative probability of flare. Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥ 20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. These findings indicate that serum sCD226 levels are associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.


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