Clinical Significance Of Serum Levels Research Articles

Clinical significance of serum levels of Saccharomyces cerevisiae IgA, IgG and perinuclear antineutrophil cytoplasmic antibodies in the differential diagnosis of inflammatory bowel diseases

Clinical significance of serum levels of Saccharomyces cerevisiae IgA, IgG and perinuclear antineutrophil cytoplasmic antibodies in the differential diagnosis of inflammatory bowel diseases

Baseline interleukin-6 is a prognostic factor for patients with metastatic breast cancer treated with eribulin

PurposeEribulin is a unique anti-cancer drug which can improve overall survival (OS) of patients with metastatic breast cancer (MBC), probably by modulating the tumor immune microenvironment. The aim of this study was to investigate the clinical significance of serum levels of immune-related and inflammatory cytokines in patients treated with eribulin. Furthermore, we investigated the association between cytokines and immune cells, such as myeloid-derived suppressor cells (MDSCs) and cytotoxic and regulatory T cells, to explore how these cytokines might affect the immune microenvironment.MethodsSixty-eight patients with MBC treated with eribulin were recruited for this retrospective study. The relationship of cytokines, including interleukin (IL)-6, to progression-free survival and OS was examined. CD4+ and CD8+ lymphocyte, MDSCs and regulatory T cell levels were determined in the blood by flow cytometry analysis.ResultsIn our cohort, patients with high IL-6 at baseline had shorter progression-free survival and OS compared with those with low IL-6 (p = 0.0017 and p = 0.0012, respectively). Univariable and multivariable analyses revealed that baseline IL-6 was an independent prognostic factor for OS (p = 0.0058). Importantly, CD8+ lymphocytes were significantly lower and MDSCs were significantly higher in patients with high IL-6, compared to those with low IL-6.ConclusionBaseline IL-6 is an important prognostic factor in patients with MBC treated with eribulin. Our results show that high IL-6 is associated with higher levels of MDSCs which suppress anti-tumor immunity, such as CD8+ cells. It appears that eribulin is not particularly effective in patients with high IL-6 due to a poor tumor immune microenvironment.

Serum cold-inducible RNA-binding protein levels as a potential biomarker for systemic sclerosis-associated interstitial lung disease

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrotic, inflammatory, and vascular dysfunction. Danger-associated molecular patterns (DAMPs)-mediated inflammasome activation has been reported to be involved in the pathogenesis of SSc. Cold-inducible RNA-binding protein (CIRP) is newly identified as a DAMP. Here we examined the clinical significance of serum levels of CIRP in 60 patients with SSc and 20 healthy control patients (HCs) using an enzyme-linked immunosorbent assay. Serum CIRP levels in diffuse cutaneous SSc (dcSSc) patients were significantly increased compared with limited cutaneous SSc (lcSSc) patients or HCs. When examining the relationship with SSc-specific parameters, serum CIRP levels with the presence of interstitial lung disease (ILD) were higher than those without ILD. In detail, serum CIRP levels correlated negatively with the percent predicted diffusing capacity for carbon monoxide and positively with levels of Krebs von den Lungen-6. In addition, elevated serum CIRP levels declined along with decreased SSc-ILD activity in patients who received immunosuppressive therapy. These results suggest that CIRP may play a role in the development of ILD in SSc. Moreover, CIRP could serve as a useful serological marker of SSc-ILD in terms of disease activity and therapeutic effects.

Clinical significance of serum levels of 14-3-3β protein in patients with stable chronic obstructive pulmonary disease

Nowadays, the diagnosis and treatment of COPD are often based on the results of lung function tests. Certain individuals, however, are not candidates for lung function testing due to pulmonary bullae, cardiac failure, low lung function, and other factors. Therefore, we evaluated whether serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) could be a biomarker for the diagnosis of stable COPD patients. The expression of serum 14-3-3β protein was evaluated by an enzyme-linked immunosorbent assay. The association between its concentrations and clinical parameters of stable COPD patients were analyzed by correlation analysis and ROC curve. The results before propensity score matching (PSM) showed that serum 14-3-3β protein concentrations (ng/ml) in stable COPD patients were significantly higher than in healthy controls (P < 0.001). Furthermore, serum 14-3-3β protein concentrations were higher in GOLD 3&4 COPD patients compared with healthy participants, GOLD 1 and GOLD 2 COPD patients (P < 0.05), which shows that the concentration of 14-3-3β protein correlates with disease severity in stable COPD patients. After 1:1 PSM, there was also a statistically significant rise in 14–3-3 protein levels in stable COPD patients compared to healthy controls (P < 0.01). Serum 14-3-3β protein levels were positively correlated with blood neutrophil levels (P < 0.05), and negatively related to lung function parameters in stable COPD patients (P < 0.01). When the cutoff value was set at 29.53 ng/ml, the ROC curve yielded a sensitivity of 84.9% and a specificity of 68.3% for diagnosing stable COPD. The 14-3-3β protein may be a potential serum biomarker for the diagnosis of stable COPD patients, which is associated with disease severity, systemic inflammation, and small airway obstruction.

Serum Levels of Selected IL-1 Family Cytokines in Patients with Morphea.

Morphea/localized scleroderma (LoS) represents an inflammatory-sclerotic skin disease, the pathogenesis of which is not fully understood. Given the important role of IL-1 family cytokines in the development and therapy of inflammatory diseases, including systemic sclerosis, we analyzed the clinical significance of serum levels of selected IL-1 family cytokines (IL-1α, IL-1β, IL-18, IL-33, IL-37 and IL-38) in LoS patients (n = 30) using the standardized disease assessment tools and comparison to healthy controls (n = 28). We also compared the pre- and post-treatment concentrations, i.e., before and after systemic (glucocorticosteroids and/or methotrexate) and/or topical (topical glucocorticosteroids and/or calcineurin inhibitors). Our findings did not reveal significant differences in baseline IL-1α, IL-1β, IL-18, IL-33, IL-37 and IL-38 levels between LoS group and HCs; however, after treatment, there were marked changes in concentrations of IL-1α and IL-33 within LoS group as well as in comparison to HCs. We also found significant negative correlations between PGA-A and IL-1α concentration as well as between mLoSSI and IL-1α after treatment. Furthermore, we showed an inverse correlation of baseline IL-1β levels with mLoSSI scores of borderline significance. We believe that IL-1α and IL-33, as well as Il-1β, may be potential mediators and targets of interest in LoS.

Clinical significance of serum levels of osteoproteherin and sclerostin in assessment of vascular calcification in chronic kidney disease stage 3-5

To clarify the mechanisms of the effect of osteoprotegerin (OPG) and sclerostin on vascular calcification and the state of the cardiovascular system in chronic kidney disease (CKD). A total of 110 patients aged 18 to 65 years with CKD stages 35D were examined. OPG, sclerostin, intact parathyroid hormone, and serum troponin I were determined using the commercial "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" from Cloude-Clone Corp. (USA) by enzyme-linked immunosorbent assay. An increase in sclerostin and OPG levels was revealed, which significantly correlated with a decrease in glomerular filtration rate, as well as an increase in left ventricle myocardial mass index and peak systolic blood flow in the aortic arch. Changes in the regulation of bone-mineral metabolism, in which the proteins inhibitors of bone metabolism, OPG and sclerostin, as well as the interactive interaction between the vascular and skeletal systems, play a decisive role in the development of lesions of the cardiovascular system caused by vascular calcification in CKD.

Clinical significance of serum levels of anti-transcriptional intermediary factor 1-γ antibody in patients with dermatomyositis.

Dermatomyositis (DM) is an autoimmune inflammatory disease characterized by skin eruptions and myositis. Anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ Ab) is one of the most frequently detected myositis-specific autoantibodiesand adults positive for anti-TIF1-γ have markedly higher rates of malignancy. Our aim was to determine the clinical associations of anti-TIF1-γ levels in 31 Japanese adult DM patients positive for anti-TIF1-γ. We determined associations between the anti-TIF1-γ index and patient characteristics and disease severities. Sixteen patients with anti-TIF1-γ Ab had concomitant malignancies. A mild positive correlation was found between the levels of serum creatine phosphokinase at the first visit and anti-TIF1-γ levels. In contrast, there was no significant difference in the anti-TIF1-γ Ab index between patients with and without malignancy. Dysphagia tended to be observed in patients with malignancy. On sequential analysis, anti-TIF1-γ levels in patients without malignancy were lower or turned negative after treatment for DM. Ab titers tended to be sustained in patients with stage IV malignancies. Interestingly, a re-increase in the Ab titer was observed on recurrence of malignancy or increase in DM activity. Four patients were completely cured of their malignancies, and anti-TIF1-γ levels in three patients turned negative with the loss of DM activity. These data suggest that higher anti-TIF1-γ titers may not directly indicate the presence of malignancy. Nevertheless, longitudinal changes in the anti-TIF1-γ index in individual patients may partially reflect activities of both DM and malignancy.

Clinical significance of serum levels of microRNA-27a and its correlation with interleukin-10 in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning.

The aims of the present study were to examine the clinical significance of serum microRNA-27a (miR-27a) levels in patients with multiple organ dysfunction syndrome (MODS) caused by acute paraquat poisoning and to investigate the correlation between miR-27a and interleukin (IL)-10. A total of 82 patients with MODS induced by acute paraquat poisoning and 88 healthy controls were recruited in the present study. Reverse transcription-quantitative PCR was used to measure serum miR-27a expression levels in patients with MODS and the control group. IL-10 serum levels were determined using ELISA. Decreased serum miR-27a level and increased IL-10 expression levels were detected in patients with paraquat poisoning compared with healthy controls (P<0.001). A moderately negative correlation was identified between the serum expression levels of miR-27a and IL-10 (r=-0.5225; P<0.001). miR-27a expression level was found to be associated with blood urea nitrogen, partial pressure of carbon dioxide, arterial blood lactic acid, and the acute physiology and chronic health evaluation II score (APACHE II; P<0.05). The area under the curve for miR-27a was 0.946, with a sensitivity of 86.6% and specificity of 87.5% at a cutoff value of 2.10. The non-survival patient group had lower miR-27a expression levels compared with the survival group (P<0.01). Multivariate Cox regression analyses suggested miR-27a expression level and APACHE II score were independent prognostic factors for 30-day mortality (P<0.01). The present results suggested that serum miR-27a level may be a potential novel diagnostic and prognostic factor for MODS caused by paraquat poisoning. Collectively, miR-27a may be involved in the process of MODS induced by paraquat poisoning by regulating the inflammatory response.

Plasma Levels of Soluble PD-L1 Correlate With Tumor Regression in Patients With Lung and Gastric Cancer Treated With Immune Checkpoint Inhibitors.

Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and anti-programmed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.

Diagnostic and Clinical Significance of Serum Levels of D-Lactate and Diamine Oxidase in Patients with Crohn's Disease.

Background Crohn's disease (CD) is a chronic intestinal inflammatory disease. An ideal laboratory marker that can predict the prognosis in terms of relapse of the disease is clinically desirable. Methods A total of 59 CD patients were enrolled in this study. Enzyme-Linked Immunosorbent Assay (ELISA) was used to quantitatively detect the content of D-lactate (D-LA) and the diamine oxidase (DAO) levels in sera obtained from patients and 28 healthy controls. The correlation between these two biomarkers and disease activity scores was assessed. In addition, the ROC curve was used to evaluate the diagnostic accuracy of these two biomarkers. Results The levels of D-LA in the serum of CD patients in the active stage and remission stage were 16.08 ± 4.8 mg/L and 11.16 ± 3.17 mg/L, respectively, and the difference was statistically significant (t = 4.67, P < 0.001). DAO levels were significantly higher in patients with the active stage compared to controls. The levels of D-LA and DAO in CD patients were positively correlated with the disease activity (r = 0.68 and 0.53, respectively, P < 0.05). The area under the ROC curve (AUC) when CD activity was diagnosed with D-LA and DAO alone was 0.815 and 0.748, respectively. The diagnostic efficacy of the two biomarkers was not significantly different from that of the erythrocyte sedimentation (ESR) and hypersensitive C-reactive protein (CRP) (P > 0.05). However, the area under the curve was 0.861 (0.746, 0.937) when the diagnosis was performed using a combination of D-LA, DAO, CRP, and ESR, which was significantly higher than when CRP or ESR were tested alone (P < 0.05). Conclusions D-LA and DAO have a good prognostic value for CD activity. Rational combined use of biomarkers can significantly improve the diagnostic efficiency.

Analysis of Lamin B1, Vimentin and Anti-Ku86 as Prospective Biomarkers of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Infection.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and most frequently develops in patients with cirrhosis. Surveillance strategies are recommended in high-risk groups because early detection of small lesions improves the likelihood of curative treatment. This study investigated the prospective clinical significance of serum levels of anti-Ku86 and plasma levels of lamin B1and vimentin as early markers of HCC. We recruited 74 patients at Assiut University Hospital-37 with HCC and 37 with chronic liver disease (liver cirrhosis patients)-and 36 age- and sex-matched healthy controls. Lamin B1 and vimentin mRNA expression levels were evaluated by reverse transcription-PCR and serum levels of anti-Ku86 were measured by enzyme-linked immunosorbent assay. Compared with liver disease patients and controls, HCC patients showed higher levels of lamin B1 mRNA (sensitivity, 96%; specificity, 65%), vimentin mRNA (sensitivity, 94%; specificity, 92%), and anti-Ku86 (sensitivity, 94%; specificity, 80%). LaminB1 levels were significantly higher in patients with a tumor size < 2 cm than in patients with tumors 2-5 cm and >5cm in size. Lamin B1 had significant positive correlations with alpha-fetoprotein (AFP) (P=0.034) and anti-Ku86 (P=0.002). Receiver operating characteristic curves for differentiating HCCfrom liver cirrhosis revealed a higher area under the curve(AUC).for vimentin than for AFP, lamin B1, and anti-Ku86 for the diagnosis of HCC (P<0.001). Circulating levels of anti-Ku86, lamin B1,and vimentin might be potential surrogate markers of HCC, either alone or in combination with AFP. However, independent and discriminative serological biomarkers with higher sensitivity and specificity are still needed for the early detection of HCC.

Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease.

We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.

Retinol-Binding Protein 4 Predicts Lesion Volume (Determined by MRI) and Severity of Acute Ischemic Stroke.

Retinol-binding protein 4 (RBP4) is an adipocyte-secreted molecule and is associated with cardiovascular risk factors. The aim of this study was to assess the clinical significance of serum levels of RBP4 in Chinese patients with acute ischemic stroke (AIS). We sequentially screened patients with first-ever AIS who were admitted to our Hospital between September 2016 and October 2017. Serum levels of RBP4 were assayed with solid-phase sandwich ELISA, and severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. We used logistic regression models to assess the relationship between RBP4 levels and stroke risk and severity. During the inclusion period, 323 patients completed the study. Our results indicated that the median serum RBP4 levels were significantly (P < 0.001) higher in patients with AIS than in those normal cases [28.9 (IQR, 17.3-39.6) μg/ml vs. 23.7 (14.6-32.3) μg/ml]. In logistic regression analysis, for each 1 unit increase of serum level of RBP4, the unadjusted and adjusted risks of AIS increased by 4% (OR 1.04 [95% CI 1.02-1.05], P < 0.001) and 3% (1.03 [1.01-1.04], P < 0.001), respectively. At admission, 116 patients (35.9%) had a minor stroke (NIHSS < 6). In logistic regression analysis, for each 1 unit increase of serum level of RBP4, the unadjusted and adjusted risks of moderate-to-high stroke increased by 7% (OR 1.07 [95% CI 1.05-1.09], P < 0.001) and 5% (1.05 [1.02-1.07], P < 0.001), respectively. Elevated levels of RBP4 could be considered an independent diagnosis marker of AIS. Elevated levels of RBP4 were significantly associated with higher stroke severity in Chinese sample.

Association of interleukin-6 and its -174G/C promoter polymorphism with clinical and laboratory characteristics of non hepatitis C virus rheumatoid arthritis patients

BackgroundInterleukin-6 is a cytokine protein, which causes inflammation, maintains immune homeostasis and shows a role in rheumatoid arthritis pathogenesis. IL-6-174G/C promoter polymorphism may have a role in susceptibility to RA. Aim of the workTo evaluate the clinical significance of serum levels of IL-6 and its -174G/C promoter polymorphism in RA patients in comparison with the controls. Patients and methodsThis study enrolled 25 non hepatitis C virus RA patients versus 25 age and gender matched controls. Demographic, clinical and laboratory data were prospectively evaluated. Serum IL-6 level and promoter (-174G/C) genotype were determined. ResultsSerum IL-6 levels was significantly higher in RA patients compared to control subjects (p = .001), especially those with CC promoter polymorphism. There was a significant correlation between IL and 6 level and duration of morning stiffness, disease activity, hemoglobin concentration and ESR level. 15/25 patients had (-174G/G) gene promoter polymorphism, 8/25 were GC and 2/25 were CC. All controls were GG. There was significant association between gene polymorphism and age at disease onset (p = .0172), which was older in those with GG genotype (38.5 ± 10.25 years) than those with CC (33.5 ± 0.71 years) and younger in GC genotypes (27.9 ± 7.9 years). None of the other clinical, laboratory or radiological parameters would predict the IL-6 promoter polymorphism. ConclusionSerum IL-6 levels and -174G/C promoter polymorphism were higher in RA patients than in healthy controls. The positive correlation of IL-6 level with the DAS28 and duration of morning stiffness may confirm its’ increased involvement in the pathogenesis of RA and may point to the need for considering of anti-IL-6 agents in their management plan. The negative correlation of IL-6 level with the hemoglobin level may confirm IL-6 play a significant role in anemia of RA.

Establishment of cut-off value of serum pro-gastrin-releasing peptide for diagnosis of small cell lung cancer and evaluation on the clinical diagnosis efficiency

Objective: To determine critical reference value (cut-off value) of serum pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase(NSE) in the diagnosis of small cell lung cancer(SCLC). To evaluate the clinical significance of serum levels of ProGRP and NSE in diagnosis and differential diagnosis in SCLC. Methods: Three hundred and fifty-two SCLC patients, 163 non small cell lung cancer(NSCLC)patients , 193 benign pulmonary disease patients and 140 healthy people visiting in National Cancer Hospital were analyzed retrospectively from January 2014 to July 2017.The levels of serum ProGRP and NSE of people were determined using electrochemiluminescent immunoassay respectively . Reference value ranges of the makers were determined by using the method of ROC curves. Results: In NSCLC group, benign lung disease group, healthy control group and mixed group (NSCLC+ lung benign diseases+ healthy control group) as a reference, the cut-off values were 58.3, 62.3, 57.8, 61.3 ng/L. In the diagnosis and differential diagnosis of SCLC and NSCLC, benign lung diseases, healthy controls and mixed group, AUC of ProGRP was 0.940 (0.919-0.961), 0.941 (0.921-0.960), 0.959 (0.944-0.975), 0.946 (0.928-0.963) respectively. The sensitivities of ProGRP were 86.4%, 84.9%, 86.4% and 84.7% respectively. The specificities of ProGRP were 95.7%, 96.9%, 99.3%, 98% respectively. In all groups the Youden's index of ProGRP and NSE were 0.821 vs 0.612, 0.818 vs 0.674, 0.857 vs 0.810, 0.827 vs 0.674. In healthy controls, no statistically significant difference was found between ProGRP and NSE (P>0.05) in the diagnosis of AUC. However, in the remaining 3 groups, the ProGRP diagnosis of AUC was significantly greater than that of NSE (P<0.01). Compared with single marker detection, the sensitivity of combined detection of ProGRP and NSE in diagnosis of SCLC increased to 95.5%, 94%, 96.6% and 94% in each group. There was no significant difference between ProGRP and ProGRP+ NSE in the diagnosis of AUC when compared with the NSCLC group and the mixed group (P>0.05). However, when combined with a healthy control group and a benign lung disease group, the ProGRP+ NSE combination was the highest for AUC diagnosis, compared with ProGRP and NSE (P<0.01). In the SCLC ED group serum ProGRP and NSE levels[776.33(3 103.4)ng/L, 52.14(60.59)μg/L]were higher than those in the SCLC LD group[295.59(799.65)ng/L, 23.36(22.97)μg/L], respectively (all P<0.001). The serum ProGRP levels of N0, N1, N2 and N3 in TNM staging were 113.0(343.65), 167.04(724.56), 427.42(1 388.62), 735.99(1 709.95)ng/L respectively (all P<0.001). Serum ProGRP and NSE levels were not statistically different between the sex groups and the age groups (all P>0.05). Conclusion: To establish the cut-off value of serum ProGRP is helpful for the diagnosis and differential diagnosis of SCLC.

Assessment of Vitronectin, Soluble Epithelial-Cadherin and TGF-β1 as a Serum Biomarker with Predictive Value for Endometrial and Ovarian Cancers.

Extracellular matrix components, including vitronectin (VN), soluble epithelial-cadherin (sE-cadherin) and transforming growth factor-beta 1 (TGF-β1), play a key role in the invasion and metastasis of cancer. The objective of the study was to determine the clinical significance of serum levels of these molecules in patients with endometrial and ovarian cancers. Serum levels of VN, sE-cadherin and TGF-β1 in patients with endometrial (n=28) and ovarian cancers (n=40) and healthy controls (n=41) were measured by ELISA using commercial kits. A significant difference was found in VN, sE-cadherin and TGF-β1 levels between patients and healthy controls (p<0.01, p<0.01 and p<0.05, respectively). Serum VN and sE-cadherin levels were decreased significantly in both endometrial and ovarian cancer patients compared to controls (p<0.01, p<0.01, respectively). Conversely, TGF-β1 levels were increased significantly in patients with ovarian cancer as compared to controls (p<0.01). There was no significant difference between healthy controls and endometrial cancer patients. In conclusion, our study reveals that serum VN, sE-cadherin and TGF-β1 levels can be candidate targets for providing new diagnostic procedures in endometrial and ovarian cancers.

Serum neutrophil gelatinase-associated lipocalin the estimation of hospital prognosis in patients with ST-elevated myocardial infarction.

We aimed to assess the clinical significance of serum levels of neutrophil gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in patients with ST-elevated myocardial infarction (STEMI). Patients admitted within 24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on hospitalization days 1 and 12. Recurrent myocardial infarction, early post-infarction angina, acute cerebrovascular accident, and death were assessed as adverse outcomes during hospitalization. The actors associated with adverse outcome were evaluated using univariate and multivariate regression analysis. Among the 260 STEMI patients included, 32% had ≥1 adverse in-hospital outcome, and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60 years, reduced glomerular filtration rate during hospitalization, and high sNGAL on day 12 were identified as risk factors for adverse in-hospital outcome, associated with a 14% increase for each 1-year increment in age after 60 years, and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL ≥ 1.046 ng/ml indicating complicated hospitalization course. sNGAL concentration on the 12th day was associated with the existing adverse outcomes, acting as a marker of MI severity.

Serum alarm antiproteases in systemic sclerosis patients

Alarm antiproteases, i.e. secretory leukocyte protease inhibitor ad elafin, are key mediators in innate immune response and integrate innate and adaptive immunity systems. The aim of the study was to assess clinical significance of serum levels of alarm antiproteases, elafin and secretory leukocyte protease inhibitor (SLPI) in patients with systemic sclerosis (SSc). Twenty-eight patients with SSc, 25 patients with rheumatoid arthritis (RA) and 22 healthy controls were recruited. Serum elafin and SLPI levels were examined using enzyme-linked immunosorbent assay (ELISA). The patients with SSc had significantly increased serum levels of SLPI in comparison with the RA patients and the healthy controls (p<0.01), and the RA patients presented significantly higher serum levels of elafin in comparison with the controls (p=0.003). In the SSc subgroup serum SLPI level negatively correlated with diffusing capacity of the lung for carbon monoxide (DLCO) (r=−0.41, p=0.03) and total lung capacity (r=−0.42, p=0.03). Both alarm antiproteases, elafin and SLPI could be potentially implicated in the pathogenesis of SSc and SLPI may be considered a candidate for serum biomarker of lung involvement in SSc.

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status.

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5±2.8years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4±6.3ng/ml) compared to control (3.5±2.6ng/ml) (p<0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r=0.32, p=0.03) and CHAQ (r=0.37, p=0.01) and negatively with the presence of GG alleles (r=-0.48, p=0.001). The GG alleles were significantly negatively associated with C-reactive protein (r=-0.32, p=0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r=-0.28, p=0.06; r=-0.25, p=0.09 and r=-0.25, p=0.09, respectively). There is evidence of a possible influence of the -308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.

Clinical significance of tumor necrosis factor-α-863 C/A and -1031 T/C promoter polymorphisms in systemic lupus erythematosus patients: Relation to disease activity and damage

Aim of the workTo assess the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and its -863 C/A and 1031 T/C promoter polymorphism in systemic lupus erythematosus (SLE) patients and find any association to disease activity and damage. Patients and methodsForty-two female SLE patients and 30 age and gender matched healthy control were included. Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaboration Clinics-damage index were assessed. Serum TNF-α levels were measured and genotyped for TNF-α-863 C/A and 1031 T/C promoters. ResultsThe SLE patients had a mean age of 28.5±7.6years and disease duration 3.3±2.9years. The mean serum TNF-α level in the SLE patients (8.2±9.8pg/ml) was significantly higher than in the control (3.5±2.6pg/ml) (p=0.005). The TNF-α-863AA genotype was significantly frequent (52.4%) in the SLE patients compared to control (23.3%) (p=0.012). Those patients had a significantly increased proteinuria and a tendency to a higher serum TNF-α level. Patients with TNF-α-1031 CC genotype had a significantly increased serum TNF-α levels (p=0.002) and frequency of mucocutaneous manifestations (p=0.03) as well as a higher frequency of lupus nephritis (LN) compared to those with TT genotype (p=0.04). Only serum TNF-α level would predict the disease activity. ConclusionTNF-α-863 promoter gene polymorphism may be considered as a genetic marker for SLE susceptibility and its AA genotype was associated with LN and with high serum TNF-α production. The TNF-α-1031 AA genotype was related to an increased serum TNF-α level as well as to mucocutaneous manifestations and LN.