scholarly journals Aberrantly Expressed Galectin-9 is Involved in the Immunopathogenesis of anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease

2020 ◽  
Author(s):  
Lin Liang ◽  
Ya-Mei Zhang ◽  
Ya-Wen Shen ◽  
Ai-Ping Song ◽  
Wen-Li Li ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Disease Activity ◽  
Lung Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Necrotizing Myopathy ◽  
Immune Mediated

Abstract Background: Rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in patients with dermatomyositis (DM) and the impact of Gal-9 on the development of DM-ILD. Methods: Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from patients with DM. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from patients who were positive for anti-melanoma differentiation-associated gene 5 (MDA5). The effect of Gal-9 on human lung fibroblasts (MRC-5) was also investigated in vitro. Results: Serum Gal-9 levels were significantly higher in patients with DM than in those with immune-mediated necrotizing myopathy and healthy controls (p < 0.001). Higher levels of serum Gal-9 were observed in anti-MDA5-positive patients with DM than in anti-MDA5-negative patients with DM (33.8 (21.9–44.7) vs 16.2 (10.0–26.9) ng/mL, p < 0.001). Among the anti-MDA5-positive patients with DM, serum Gal-9 levels were associated with ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive patients with DM in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive patients with DM (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from patients with immune-mediated necrotizing myopathy (1.1 ± 0.3 ng/mL, p = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, p = 0.045). The mRNA levels of Gal-9 were positively correlated with levels of type-I interferon-inducible genes MX1 (r = 0.659, p = 0.020) and IFIH1 (r = 0.787, p = 0.002) in PBMCs from anti-MDA5-positive patients with DM. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. In vitro stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.Conclusions: Among anti-MDA5-positive patients with DM, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.

scholarly journals Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Lin Liang ◽  
Ya-Mei Zhang ◽  
Ya-Wen Shen ◽  
Ai-Ping Song ◽  
Wen-Li Li ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Disease Activity ◽  
Lung Disease ◽  
Longitudinal Studies ◽  
Type I ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Necrotizing Myopathy ◽  
Immune Mediated

BackgroundDermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD.MethodsA total of 154 idiopathic inflammatory myopathy patients and 30 healthy controls were enrolled in the study. Cross-sectional and longitudinal studies were used to analyze the association between serum Gal-9 levels and clinical features. Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from DM patients. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from anti-melanoma differentiation-associated gene 5 (MDA5)-positive patients. The effect of Gal-9 on human lung fibroblasts (MRC-5) was investigated in vitro.ResultsSerum Gal-9 levels were significantly higher in DM patients than in immune-mediated necrotizing myopathy patients and healthy controls (all p &lt; 0.001). Higher serum Gal-9 levels were observed in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients [33.8 (21.9–44.7) vs. 16.2 (10.0–26.9) ng/mL, p &lt; 0.001]. Among the anti-MDA5-positive DM patients, serum Gal-9 levels were associated with RP-ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive DM patients in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive DM patients (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from immune-mediated necrotizing myopathy patients (1.1 ± 0.3 ng/mL, p = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, p = 0.045). The mRNA levels of Gal-9 were positively correlated with the levels of type-I interferon-inducible genes MX1 (r = 0.659, p = 0.020) and IFIH1 (r = 0.787, p = 0.002) in PBMCs from anti-MDA5-positive DM patients. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. In vitro stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.ConclusionsAmong anti-MDA5-positive DM patients, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.

scholarly journals Increased levels of VCAM-1 in sera and VLA-4 expression on neutrophils in dermatomyositis with interstitial lung disease

2020 ◽  
Author(s):  
Meiyi Lin ◽  
Xudong Liu ◽  
Chunshu Yang ◽  
Shan Zhao ◽  
Bailing Tian ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Diffuse Alveolar Damage ◽  
Total Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
High Resolution Computed Tomography ◽  
Peripheral Blood Neutrophil ◽  
Late Antigen ◽  
And Gender

Abstract Background: Vascular cell adhesion molecule-1(VCAM-1) and its ligand very late antigen (VLA-4) play important roles in many autoimmune diseases. Our study aimed to investigate serum VCAM-1 level and VLA-4 expression on peripheral blood neutrophil surface in patients with dermatomyositis (DM), especially focusing on patients with interstitial lung disease(ILD). Methods: Blood specimens of 30 patients with DM and 30 healthy controls matched for age and gender were recruited. Total serum VCAM-1 level was measured using commercial enzyme-linked immunosorbent assay (ELISA) and the percentages of VLA-4 expression on the surface of neutrophils were analyzed by flow cytometry. We divided patients into subgroups according to whether they had ILD and whether they exhibited diffuse alveolar damage (DAD) via high-resolution computed tomography (HRCT).Results: Serum VCAM-1 levels were increased in DM patients compared with healthy controls (p<0.001). Patients with DM-ILD had higher serum VCAM-1 levels than those with none-ILD (p=0.015). The VCAM-1 levels were significantly increased in the DM-DAD group compared to the none-DAD group (p=0.002). The percentages of VLA-4 expression on neutrophils surface in DM patients were significantly elevated than that in healthy controls (p<0.001). The percentage of VLA-4 expression on neutrophils in DM patients with ILD were higher than none-ILD group(p=0.013). In the patients with ILD, DAD group had higher percentage of VLA-4 expression on neutrophils than none-DAD group (p=0.008).Conclusions: Our findings indicated that serum VCAM-1 level could be used as a potential serological biomarker for DM-ILD.

Effect of MMP-13 degraded SPARC on type I collagen and its biomarker potential in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 717-717
Author(s):  
Stephanie Nina Kehlet ◽  
Henrik Harling ◽  
Lars N Jørgensen ◽  
Morten A Karsdal ◽  
Nicholas Willumsen
Keyword(s):  
Colorectal Cancer ◽  
Type I Collagen ◽  
Collagen Degradation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matricellular Protein ◽  
Elisa Assay ◽  
Type I ◽  
Healthy Controls ◽  
Collagen Deposition

717 Background: Increased collagen deposition and remodeling of the extracellular matrix has been shown to play a role in the pathology of gastrointestinal cancer (GC). The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) binds collagens and hereby regulates collagen fibrillogenesis. Matrix metalloproteinase (MMP) mediated cleavage of SPARC, increases the affinity for collagens up to 20-fold. SPARC has been shown to be overexpressed in GC patients and associated with GC cell invasion and metastasis. Increased expression and cleavage of SPARC might therefore be implicated in GC pathology by increasing collagen deposition. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific MMP-13 generated fragment of SPARC - a cleavage site involved in increased collagen affinity. The biomarker potential of this fragment was examined in serum from colorectal cancer (CRC) patients and healthy controls. Moreover, we evaluated the ability of cleaved SPARC to prevent type I collagen degradation in vitro. Methods: A monoclonal antibody was raised against a MMP-13-generated neo-epitope of SPARC and a competitive ELISA assay (SPARC-M) was developed and technically validated. Serum levels were assessed in CRC patients (n=50) and healthy controls (n=30). The ability of cleaved SPARC to prevent collagen degradation was investigated using an ELISA assay measuring type I collagen degradation by MMP-9. Results: SPARC-M was technically robust and specific for SPARC cleaved by MMP-13. The fragment was elevated in CRC patients when compared to healthy controls (p=0.0097). When MMP-13 degraded SPARC was incubated with type I collagen and MMP-9, type I collagen degradation was completely inhibited suggesting that SPARC increases collagen deposition by preventing collagen degradation. Conclusions: SPARC-M was significantly elevated in CRC patients compared to healthy controls suggesting biomarker potential. Biologically, cleaved SPARC may prevent type I collagen degradation hereby leading to a pro-tumorigenic environment. Larger clinical studies are needed to validate the clinical use of this biomarker in GC.

scholarly journals Increased levels of HE4 (WFDC2) in systemic sclerosis: a novel biomarker reflecting interstitial lung disease severity?

2020 ◽  
Vol 11 ◽  
pp. 204062232095642
Author(s):  
Mingxia Zhang ◽  
Liyun Zhang ◽  
Linning E ◽  
Ke Xu ◽  
Xu Fei Wang ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Lavage Fluid ◽  
Ct Scans ◽  
Function Parameter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
High Resolution Computed Tomography

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.

scholarly journals Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease

2021 ◽  
Vol 10 (14) ◽  
pp. 3167
Author(s):  
Eva Cabrera Cesar ◽  
Lidia Lopez-Lopez ◽  
Estrella Lara ◽  
M. Victoria Hidalgo-San Juan ◽  
Concepcion Parrado Romero ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Connective Tissue Disease ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls

Introduction: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. Results: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86–1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60–0.97). Conclusion: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.

scholarly journals Soluble Programmed Death Molecule 1 (sPD-1) As Predictor of Interstitial Lung Disease in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Li Xu ◽  
Lichun Jiang ◽  
Liuyan Nie ◽  
Songzhao Zhang ◽  
Lie Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Logistic Regression Analysis ◽  
Multivariate Logistic Regression Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Programmed Death

Abstract Objective To determine the relationship between serum soluble programmed death molecule-1 (sPD-1) levels and the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Methods Blood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by enzyme-linked immunosorbent assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis. Results Serum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P = 0.01, r = − 0.354), total lung capacity % (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689. Conclusion Serum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.

scholarly journals Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

2020 ◽  
Author(s):  
Yueyan Lou ◽  
yu zheng ◽  
Xiaoming Tan ◽  
Bijun Fan ◽  
Liyan Zhang ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Serum Levels ◽  
Clinical Severity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Disorder ◽  
Healthy Controls ◽  
Serum Samples ◽  
High Resolution Computed Tomography ◽  
Highly Correlated

Abstract Background: Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. Methods: Serum samples of 40 DM-ILD patients and 30 healthy controls were collected. Expressions of S100A8/A9 were analyzed by enzyme-linked immunosorbent assay (ELISA) and interleukins were analyzed by cytometric beads array (CBA). Results: Serum IL-4, IL-6 and S100A8/A9 were observably higher in DM-ILD than those in healthy controls ( p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls ( p = 0.0001). IL-4 ( r = 0.1171, p = 0.0040), IL-6 ( r = 0.1174, p = 0.0040) and IL-10 ( r = -0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) ( r = 0.1642, p = 0.0157) and lung function (DLCO%: r = -0.2066, p = 0.0061, FVC%: r = -0.2156, p = 0.0050). Conclusions: Serum level of S100A8/A9 may be a valuable marker for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD. Keywords : Dermatomyositis, Interstitial lung disease, S100A8/A9, Interleukin

scholarly journals Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongpeng Ge ◽  
Hanbo Yang ◽  
Xinyue Xiao ◽  
Lin Liang ◽  
Xin Lu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Signal Recognition Particle ◽  
Ground Glass Opacity ◽  
Signal Recognition ◽  
High Resolution Computed Tomography ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Long Term Follow Up

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients. Conclusions ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.

scholarly journals Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in rheumatoid arthritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Li Xu ◽  
Lichun Jiang ◽  
Liuyan Nie ◽  
Songzhao Zhang ◽  
Lei Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Logistic Regression Analysis ◽  
Multivariate Logistic Regression Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Programmed Death

Abstract Background Previous studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD. Methods Blood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis. Results Serum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P  = 0.01, r = − 0.354), total lung capacity (TLC%) (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689. Conclusion Serum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.

scholarly journals AB0410 S100A4 PLASMA LEVELS CORRELATE WITH DISEASE ACTIVITY, SKIN FIBROSIS AND INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1233.2-1233
Author(s):  
H. Štorkánová ◽  
L. Andres Cerezo ◽  
S. Oreska ◽  
M. Špiritović ◽  
B. Heřmánková ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Disease Activity ◽  
Lung Disease ◽  
Plasma Levels ◽  
Statistical Significance ◽  
Activity Score ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Peripheral Oxygen Saturation ◽  
Potential Association

Background:In our previous study we demonstrated that S100A4 is overexpressed in scleroderma (SSc) skin, SSc fibroblasts and preclinical models of SSc in a TGF-β dependent manner. We showed that S100A4 is a new regulator of TGF-β signalling and its inhibition prevents the pro-fibrotic effects of TGF-β. Inactivation of S100A4 prevented dermal fibrosis induced by bleomycin and in Tsk-1 miceObjectives:The aim of this study was to evaluate S100A4 in the peripheral blood of SSc patients and characterize its potential association with SSc-related features.Methods:A total of 33 patients (29 females; mean age 52.8; disease duration 4.2 years; dcSSc/lcSSc = 8/25) who met the 2013 EULAR/ACR classification criteria for SSc and 20 healthy age- and sex-matched individuals were included in this study. Plasma levels of S100A4 were measured using ELISA (CUSABIO, Houston, USA). Data are presented as median (IQR).Results:S100A4 plasma levels were significantly increased in SSc patients compared to healthy controls (78.6(32.3-146.5) vs. 43.4(32.3-53.4)ng/mL,p=0.011). Patients with diffuse cutaneous (dc)SSc had significantly higher levels of S100A4 than patients with limited cutaneous (lc)SSc or healthy controls (168.5(81.5-347.5) vs. 63.4(30.9-130.6),p=0.017,p=0.001, respectively). Plasma levels of S100A4 positively correlated with mRSS (r=0.556,p=0.001). Furthermore, S100A4 negatively correlated with forced vital capacity (FVC) and peripheral oxygen saturation (SpO2) (r=- 0.362,p=0.038;r=-0.414,p=0.029, respectively). S100A4 levels positively correlated with ESSG activity score (r=0.750,p<0.001). However, only correlations between S100A4 and mRSS, and ESSG activity score were approved at corrected level of statistical significance after Bonferroni’s correction (p<0.01). In a prospective analysis of patients (n=40) with progressive SSc-ILD treated with 6 (n=24) or 12 (n=16) monthly i.v. pulses of cyclophosphamide (CPA, 500 mg/m2), we observed a significant decrease in plasma S100A4 levels between the baseline samples (month 0) and blood drawn after 6 months of CPA treatment (76.3(52.9–98.6) vs. 73.2(44.4–98.6)ng/mL,p=0.013). Furthermore, baseline S100A4 levels predicted the change (m0-m6) in CRP and ESR levels after 6 months of CPA therapy (r=0.472,p=0.004;r=0.528,p=0.003, respectively).Conclusion:We demonstrate that plasma S100A4 levels are significantly increased in SSc patients compared with healthy controls. Increased S100A4 is associated with the dcSSc subset, skin involvement, deteriorated parameters of interstitial lung disease and higher disease activity. In patients with progressive SSc-ILD, S100A4 declines after 6 months of cyclophosphamide therapy and predicts the systemic inflammatory response. These data further support our previous findings on the role of S100A4 as a regulator of TGF-β induced fibrosis in SSc.Acknowledgements:Supported by MHCR023728, SVV–260373.Disclosure of Interests:None declared

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