Use of Serum Clara Cell 16-kDa (CC16) Levels as a Potential Indicator of Active Pulmonary Fibrosis in Systemic Sclerosis

2011 ◽  
Vol 38 (5) ◽  
pp. 877-884 ◽  
Author(s):  
MINORU HASEGAWA ◽  
MANABU FUJIMOTO ◽  
YASUHITO HAMAGUCHI ◽  
TAKASHI MATSUSHITA ◽  
KATSUMI INOUE ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Lupus Erythematosus ◽  
Characteristic Curve ◽  
Serum Levels ◽  
Clara Cell ◽  
Inactive Disease ◽  
Surfactant Protein D ◽  
Healthy Controls

Objective.To clarify the clinical significance of concentrations of serum Clara cell 16-kDa protein (CC16; previously denoted CC10) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc); and to compare CC16 levels with levels of the current most reliable serum markers for PF, such as Krebs von den Lungen-6 (KL-6) antigen and surfactant protein-D (SP-D).Methods.Serum levels of CC16, KL-6, and SP-D were determined by ELISA in 92 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. In a retrospective longitudinal study, correlation of serum CC16 levels with the activity of PF was assessed in 16 SSc patients with PF.Results.Although CC16 levels were higher in patients with SSc than in SLE patients or healthy controls, the difference was not significant. Increased serum CC16 levels were associated with involvement of PF, especially active PF, as well as KL-6 and SP-D. Receiver operating characteristic curve analysis revealed that the utility of CC16 is slightly inferior to KL-6, but was comparable with that of SP-D for detecting PF in patients with SSc. In the longitudinal study, serum levels of CC16, KL-6, and SP-D were significantly decreased in the inactive disease phase compared to the active disease phase.Conclusion.CC16 levels can be used as a potential serum biomarker for PF in addition to KL-6 and SP-D in patients with SSc.

Elevated Circulating TWEAK Levels in Systemic Sclerosis: Association with Lower Frequency of Pulmonary Fibrosis

2009 ◽  
Vol 36 (8) ◽  
pp. 1657-1662 ◽  
Author(s):  
KOICHI YANABA ◽  
AYUMI YOSHIZAKI ◽  
EIJI MUROI ◽  
TOSHIHIDE HARA ◽  
FUMIHIDE OGAWA ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Lupus Erythematosus ◽  
Tumor Necrosis ◽  
Vital Capacity ◽  
Protective Factor ◽  
Serum Levels ◽  
Clinical Associations ◽  
Necrosis Factor

Objective.To determine serum levels of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) and its clinical associations in patients with systemic sclerosis (SSc).Methods.Serum TWEAK levels from 70 patients with SSc were examined by ELISA. In a retrospective longitudinal study, sera from 23 patients with SSc were analyzed (followup 0.8–7.2 yrs).Results.Serum TWEAK levels were elevated in patients with SSc (n = 70) compared with healthy controls (n = 31) and patients with systemic lupus erythematosus (n = 22). Among patients with SSc, there were no differences in serum TWEAK levels between limited cutaneous SSc and diffuse cutaneous SSc. Patients with SSc who had elevated TWEAK levels less often had pulmonary fibrosis and decreased vital capacity than those with normal TWEAK levels. In the longitudinal study, SSc patients with inactive pulmonary fibrosis or without pulmonary fibrosis consistently exhibited increased TWEAK levels, while those with active pulmonary fibrosis showed decreased TWEAK levels during the followup period.Conclusion.TWEAK levels were increased in patients with SSc, and associated with a lower frequency of pulmonary fibrosis in patients with SSc. TWEAK could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.

scholarly journals Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Vinod Umare ◽  
Vandana Pradhan ◽  
Milind Nadkar ◽  
Anjali Rajadhyaksha ◽  
Manisha Patwardhan ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Organ Damage ◽  
Inactive Disease ◽  
Control Group ◽  
Healthy Controls ◽  
Sledai Score ◽  
Active Disease

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1βwere found to be significantly higher in SLE patients than healthy controls (P<0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P=0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-αwas44.76±68.32 pg/mL for patients with active disease while it was25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P=0.0161). Similar results were obtained for IL-1β(P=0.0002). Correlation between IL-6, TNF-α, and IL-1βserum levels and SLEDAI score was observed (r=0.20,r=0.27, andr=0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: a cross-sectional human study

Lupus ◽  
2017 ◽  
Vol 26 (9) ◽  
pp. 975-982 ◽  
Author(s):  
M Sahebari ◽  
G Roshandel ◽  
N Saadati ◽  
M Saghafi ◽  
N Abdolahi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Human Study ◽  
Serum Levels ◽  
Inactive Disease ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Positive Correlation ◽  
Active Patients

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta –0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.

Elevated Serum Concentrations of Polymorphonuclear Neutrophilic Leukocyte Elastase in Systemic Sclerosis: Association with Pulmonary Fibrosis

2009 ◽  
Vol 36 (1) ◽  
pp. 99-105 ◽  
Author(s):  
TOSHIHIDE HARA ◽  
FUMIHIDE OGAWA ◽  
KOICHI YANABA ◽  
YOHEI IWATA ◽  
EIJI MUROI ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Elevated Serum ◽  
Serum Levels ◽  
Oxidative Stress Marker ◽  
Surfactant Protein D ◽  
Serum Concentrations ◽  
Leukocyte Elastase ◽  
Pmn Elastase ◽  
Pmn Élastase

ObjectiveTo determine the serum concentrations and clinical association of polymorphonuclear neutrophilic leukocyte (PMN) elastase in patients with systemic sclerosis (SSc).MethodsSerum PMN elastase levels from 21 patients with limited cutaneous SSc (lSSc) and 32 with diffuse cutaneous SSc (dSSc) were examined by ELISA.ResultsSerum PMN elastase levels were elevated in patients with SSc, especially dSSc, compared to healthy controls. SSc patients with elevated serum PMN elastase levels had more frequent presence of pulmonary fibrosis, arthritis, contracture of phalanges, and diffuse pigmentation. Anticentromere antibody was detected less frequently in SSc patients with elevated serum PMN elastase levels than in controls. Consistently, serum PMN elastase levels also correlated positively with serum levels of KL-6 and surfactant protein-D, serological markers for pulmonary fibrosis. Serum PMN elastase levels were also associated with levels of serum 8-isoprostane, an oxidative stress marker in SSc.ConclusionSerum PMN elastase levels were elevated in patients with SSc, and it was more prominent in patients with pulmonary fibrosis, suggesting that serum PMN elastase is a novel serological marker for SSc-related pulmonary fibrosis.

scholarly journals S100A9/CD163 expression profiles in classical monocytes as biomarkers to discriminate idiopathic pulmonary fibrosis from idiopathic nonspecific interstitial pneumonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masahiro Yamashita ◽  
Yuh Utsumi ◽  
Hiromi Nagashima ◽  
Hiroo Nitanai ◽  
Kohei Yamauchi
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Healthy Volunteers ◽  
Interstitial Pneumonia ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Serum Levels ◽  
Surfactant Protein D ◽  
Nonspecific Interstitial Pneumonia ◽  
Classical Monocytes

AbstractCirculating monocytes have pathogenic relevance in idiopathic pulmonary fibrosis (IPF). Here, we determined whether the cell surface levels of two markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, expressed on CD14strongCD16− classical monocytes by flow cytometry could discriminate IPF from idiopathic nonspecific interstitial pneumonia (iNSIP). Twenty-five patients with IPF, 25 with iNSIP, and 20 healthy volunteers were prospectively enrolled in this study. The S100A9+CD163− cell percentages in classical monocytes showed a pronounced decrease on monocytes in iNSIP compared to that in IPF. In contrast, the percentages of S100A9−CD163+ cells were significantly higher in iNSIP patients than in IPF patients and healthy volunteers. In IPF patients, there was a trend toward a correlation between the percentage of S100A9+CD163− monocytes and the surfactant protein-D (SP-D) serum levels (r = 0.4158, [95% confidence interval (CI) − 0.02042–0.7191], p = 0.051). The individual percentages of S100A9+CD163− and S100A9−CD163+ cells were also independently associated with IPF through multivariate regression analysis. The unadjusted area under the receiver operating characteristic curve (ROC-AUC) to discriminate IPF from iNSIP was (ROC-AUC 0.802, 95% CI [0.687–0.928]), suggesting that these are better biomarkers than serum SP-D (p < 0.05). This preliminary study reports the first comparative characterization of monocyte phenotypes between IPF and iNSIP.

Increased Serum Levels of Nɛ-(hexanoyl)lysine, A New Marker of Oxidative Stress, in Systemic Sclerosis

2008 ◽  
Vol 35 (11) ◽  
pp. 2214-2219 ◽  
Author(s):  
KAZUHIRO SHIMIZU ◽  
FUMIHIDE OGAWA ◽  
YUICHIRO AKIYAMA ◽  
EIJI MUROI ◽  
AYUMI YOSHIZAKI ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systemic Sclerosis ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Igg Antibody ◽  
Agalactosyl Igg ◽  
Immunological Abnormalities

ObjectiveTo determine serum levels of Nɛ-(hexanoyl)lysine (HEL), a new marker of oxidative stress, and its clinical association in patients with systemic sclerosis (SSc).MethodsSerum HEL levels from 26 patients with limited cutaneous SSc (lSSc), 34 with diffuse cutaneous SSc (dSSc), 20 with systemic lupus erythematosus (SLE), 20 with dermatomyositis (DM), and 40 healthy individuals were examined by enzyme linked immunosorbent assay.ResultsSerum HEL levels were elevated in patients with SSc compared with healthy controls (n = 40) with similar levels between patients with lSSc and dSSc (p < 0.0001). SSc patients with elevated HEL levels had increased serum levels of anti-agalactosyl IgG antibody, rheumatoid factor (RF), and IgM than those with normal HEL levels (p < 0.05). HEL levels correlated positively with anti-agalactosyl IgG antibody (p = 0.013, r = 0.408) and RF titer (p = 0.0028, r = 0.426).ConclusionOur results suggest that oxidative stress may play an important role in immunological abnormalities of SSc, especially in the production of autoantibodies including anti-agalactosyl IgG antibody and RF.

scholarly journals Female sexual dysfunction in systemic sclerosis: The role of endothelial growth factor and endostatin

2018 ◽  
Vol 4 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Antonietta Gigante ◽  
Luca Navarini ◽  
Domenico Margiotta ◽  
Biagio Barbano ◽  
Antonella Afeltra ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Blood Flow ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Sexual Dysfunction ◽  
Resistive Index ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Endothelial Growth Factor

Introduction: Since female sexual dysfunction in systemic sclerosis women is multifactorial, we can assume that vascular damage may play a role in pathogenesis. The aim of the study was to evaluate the clitoral blood flow, by Echo color Doppler, and to correlate it whit serum levels of vascular endothelial growth factor and endostatin. Methods: A total of 15 systemic sclerosis women and 10 healthy controls matched for sex and age were enrolled in this study. Serum VEGF165 and endostatin levels were determined in systemic sclerosis patients by commercial enzyme-linked immunosorbent assay kit. Clitoral blood flow was measured by Doppler indices of clitoral artery: pulsatile index, resistive index, and systolic/diastolic ratio were measured. Sexual dysfunction was assessed by Female Sexual Function Index. Results: Vascular endothelial growth factor (pg/mL) and endostatin (ng/mL) median values were significantly higher in systemic sclerosis women than healthy controls. Resistive index and systolic/diastolic ratio median values were significantly higher in systemic sclerosis women than healthy controls. Negative correlation exists between serum levels of vascular endothelial growth factor and resistive index (r = −0.55, p < 0.05). Positive correlation was observed between serum levels of endostatin and resistive index (r = 0.70, p < 0.01) and systolic/diastolic ratio (r = 0.77, p < 0.01). Discussion: We can suppose that clitoral blood flow in systemic sclerosis women is reduced not only for macro- and microvascular damage but also for impaired angiogenesis.

Anti–α-enolase antibody combined with β2 microglobulin evaluated the incidence of nephritis in systemic lupus erythematosus patients

Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Y Huang ◽  
L Chen ◽  
K Chen ◽  
F Huang ◽  
Y Feng ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Correlation Analysis ◽  
Lupus Erythematosus ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Β2 Microglobulin ◽  
Potential Indicator ◽  
Operating Characteristic Curve

Objective Anti–α-enolase antibody (Ab) combined with β2 microglobulin (β2-MG) were investigated to predict the incidence of nephritis in systemic lupus erythematosus (SLE) patients. Methods Levels of serum anti–α-enolase Ab and urinary β2-MG were detected in 115 SLE patients, 29 SLE patients with nephritis and 70 healthy controls by ELISA and immunoturbidimetry, respectively. Furthermore, the correlation between anti–α-enolase Ab combined with β2-MG and the incidence of nephritis in SLE patients was evaluated by correlation analysis. Results The optical density value of serum anti–α-enolase Ab in SLE patients with nephritis (0.84) was greatly increased compared with SLE patients (0.76) or healthy controls (0.54). Moreover, the levels of urinary β2-MG in SLE patients with nephritis (6.75 mg/L) were increased compared with SLE patients (3.45 mg/L) or healthy controls (1.48 mg/L). There was a positive correlation between the level of anti–α-enolase Ab and β2-MG ( r = 0.754). Furthermore, anti–α-enolase Ab combined with β2-MG for evaluating the incidence of nephritis in SLE patients had the best assessment of the effectiveness (area under the receiver operating characteristic curve (AUC): 92.7%) compared with only anti–α-enolase Ab (AUC: 80.9%) or β2-MG (AUC: 84.5%). Conclusion These data suggested that anti–α-enolase Ab may be a potential indicator for the prediction of nephritis in SLE patients.

scholarly journals The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tetsuya Hanaka ◽  
Takashi Kido ◽  
Shingo Noguchi ◽  
Sohsuke Yamada ◽  
Hirotsugu Noguchi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Healthy Volunteers ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Lung Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Inflammatory Changes

Abstract Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. Methods Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. Results Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. Conclusions PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.

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