scholarly journals Plasma Soluble CD146 as a Potential Diagnostic Marker of Acute Rejection in Kidney Transplantation

2020 ◽  
Vol 7 ◽  
Author(s):  
Jun Liao ◽  
Qian Fu ◽  
Wenfang Chen ◽  
Jun Li ◽  
Wenhui Zhang ◽  
...  

Previous studies have implicated the role of CD146 and its soluble form (sCD146) in the pathogenesis of inflammatory diseases. However, the association between CD146 and acute rejection in kidney transplant patients remains unexplored. In this study, fifty-six patients with biopsy-proved rejection or non-rejection and 11 stable allograft function patients were retrospectively analyzed. Soluble CD146 in plasma was detected in peripheral blood by enzyme linked immunosorbent assay (ELISA), and local CD146 expression in graft biopsy was detected by immunohistochemistry. We found that plasma soluble CD146 in acute rejection recipients was significantly higher than in stable patients without rejection, and the biopsy CD146 staining in the rejection group was higher than that of the non-rejection group. Multivariate analysis demonstrated soluble CD146 as an independent risk factor of acute rejection. The area under the receiver operating characteristic curve (AUC) of sCD146 for AR diagnosis was 0.895, and the optimal cut-off value was 75.64 ng/ml, with a sensitivity of 87.8% and a specificity of 80.8%, which was better than eGFR alone (P = 0.02496). Immunohistochemistry showed CD146 expression in glomeruli was positively correlated with the Banff-g score, and its expression in tubules also had a positive relationship with the Banff-t score. Therefore, soluble CD146 may be a potential biomarker of acute rejection. Increased CD146 expression in the endothelial or tubular epithelial cells may imply that endothelial/epithelial dysfunction is involved in the pathogenesis of immune injury.

2020 ◽  
Vol 21 (6) ◽  
pp. 2040 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Mariusz Gryko ◽  
Piotr Mroczko ◽  
Agnieszka Kulczyńska-Przybik ◽  
...  

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.


Author(s):  
Yukari Kajiura ◽  
Jung-Hwan Lew ◽  
Takahisa Ikuta ◽  
Yasufumi Nishikawa ◽  
Jun-ichi Kido ◽  
...  

Background Periodontitis is an inflammatory disease. The aim of this study was to investigate whether the soluble form of interleukin-6 receptor (sIL-6R) and calprotectin concentrations in gingival crevicular fluid are useful biomarkers in the evaluation of periodontitis. Methods First, a cross-sectional study was performed. A total of 34 periodontitis patients were enrolled and the gingival crevicular fluid samples were collected from the healthy and inflamed sites of periodontal pockets in each patient. The relationship between periodontal condition and gingival crevicular fluid sIL-6R and calprotectin concentrations was analysed statistically. The cut-off values of gingival crevicular fluid sIL-6R and calprotectin concentrations for the evaluation of periodontitis were determined using a receiver operating characteristic curve. Next, by using enzyme-linked immunosorbent assay, it was examined whether calprotectin induces sIL-6R production in THP-1 macrophages. Results Both gingival crevicular fluid sIL-6R and calprotectin concentrations were significantly higher in the inflamed sites than in the healthy sites ( P < 0.0001). The cut-off values of gingival crevicular fluid sIL-6R and calprotectin concentrations for the evaluation of periodontal inflammation were as follows: sIL-6R: 43.5 pg/site; calprotectin: 134.3 ng/site. In the in vitro study, calprotectin significantly induced sIL-6R production in THP-1 macrophages ( P < 0.01). Conclusions Both gingival crevicular fluid sIL-6R and calprotectin concentrations are significant biomarkers in the evaluation of periodontal inflammation.


2020 ◽  
Author(s):  
Hayoung Choi ◽  
Yousang Ko ◽  
Chang Youl Lee

Abstract Background Malignant pleural effusion (MPE) is a common complication of lung cancer and intrathoracic spreading or metastasis of extra-thoracic malignancy. The aim of the present study was to evaluate the levels of pro-cathepsin D from plasma and pleural fluid in patients with MPE and those in patients with benign pleural effusion (BPE) including pleural tuberculosis and parapneumonic effusion.Methods This study included 81 patients with pleural effusion who underwent thoracentesis and pleural biopsy. Pleural fluid and serum were collected as a standard procedure for all individuals at the same time. The level of pro-cathepsin D was measured by the sandwich enzyme-linked immunosorbent assay method.Results Though there were no significant differences in plasma pro-cathepsin D between the two groups, the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group (0.651 versus 0.590 pg/mL, P = 0.034) (Table 1). In addition, there were no differences in pleural fluid pro-cathepsin D level according to causative malignancy of MPE. On receiver operating characteristic curve analysis, the optimal discrimination point between the MPE group and BPE group was defined as a cut-off value of 0.5960 pg/mL for pleural fluid pro-cathepsin D (81.0% sensitivity; 53.0% specificity) and 0.4335 pg/mL for plasma pro-cathepsin D (71.4% sensitivity; 61.7% specificity).Conclusions We found that the level of pleural fluid pro-cathepsin D was significantly higher in the MPE group than the BPE group. Pro-cathepsin D could be a novel and potential biomarker to discriminate MPE from BPE.


2020 ◽  
Author(s):  
Hongxiang Lu ◽  
Anqiang Zhang ◽  
Dalin Wen ◽  
Juan Du ◽  
Jianhui Sun ◽  
...  

Abstract BackgroudVanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 expression can be used to predict traumatic sepsis in an early time.MethodsIn this three-stage prospective cohort study, severe trauma patients admitted to two hospitals from January 2015 to October 2018 were enrolled. Clinical data during hospitalization and APACHE II score were collected. Plasma vanin-1 levels were measured by enzyme linked immunosorbent assay. The associations among variables and traumatic sepsis were identified by logistic regression model. The receiver-operating characteristic curve was analyzed to evaluate the diagnostic efficiency of the selected factors.ResultsA total of 426 trauma patients (22 patients in the discovery cohort, 283 patients in the internal test cohort, and 121 patients in the external validation cohort) and 16 healthy volunteers were enrolled. The plasma vanin-1 level of trauma patients was significantly higher than that of healthy volunteers (P < 0.05), and sepsis patients had higher plasma vanin-1 than non-sepsis patients in the discovery trauma cohort (P < 0.05). In the internal test cohort, plasma vanin-1 levels at day 1 after trauma were significantly associated with the incidence of sepsis (OR = 3.92, 95% CI = 2.68–5.72, P = 1.62⊆10− 12). As a predictive biomarker, vanin-1 obtained a better area under the curve (AUC) (0.82, 95% CI = 0.77–0.87) than C-reaction protein (CRP) (0.62, 95% CI = 0.56–0.68, P < 0.0001), procalciton in (PCT) (0.66, 95% CI = 0.60–0.71, P < 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI = 0.65–0.76, P = 6.70⊆10− 3). In addition, the clinical relevance between plasma vanin-1 and traumatic sepsis was validated in the external validation cohort (OR = 4.26, 95% CI = 2.22–8.17, P = 1.28⊆10− 5). The AUC of vanin-1 was 0.83 (95% CI = 0.75–0.89), which was better than that of CRP, PCT, and APACHE II.ConclusionsOur study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis.Trial registrationClinicaltrials.gov Identifier NCT01713205. Registered 24 October 2012.


2018 ◽  
Vol 32 (5) ◽  
pp. 380-387 ◽  
Author(s):  
Abigail Pulsipher ◽  
Brock M. Davis ◽  
Kristine A. Smith ◽  
Shaelene Ashby ◽  
Xuan Qin ◽  
...  

Background Calgranulin C (S100A12) is an innate immune peptide at the air–mucosal interface associated with neutrophil involvement, which when overexpressed has been implicated as a biomarker of inflammatory diseases. Decreased epithelial expression of certain innate immune peptides has been reported in chronic rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in the sinonasal mucosa of patients with CRS compared to controls and that S100A12 is a potential biomarker of CRS-specific quality of life (QOL) and disease severity. Methods A prospective observational study was conducted which included 70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP) nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was assessed in the anterior ethmoid tissues from all patients using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease-specific QOL (Rhinosinusitis Disability Index) and disease severity (computed tomography [CT] and endoscopy) were evaluated and correlated to the expression levels of S100A12. Results S100A12 and HNE were significantly elevated in patients with CRSsNP compared to normal controls ( P < .05 and P < .001, respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS-specific disease severity compared to normal controls ( P < .05), and the increased protein levels of S100A12 were significantly correlated to disease severity, represented by CT scores ( P < .05). Conclusions S100A12 is differentially expressed in CRS subtypes and is significantly elevated in patients with CRSsNP and associated with CRS-specific disease severity.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Wang ◽  
Zhaohui Zheng ◽  
Yuxian Yang ◽  
Jianan Lang ◽  
Ning Zhang ◽  
...  

Abstract Background Circulating angiopoietin-like 2 (ANGPTL2) protein levels are known to be significantly increased in numerous chronic inflammatory diseases and are associated with the diagnosis and/or prognosis of cardiovascular diseases, diabetes, chronic kidney disease, and various types of cancers. However, no data regarding the relationship between ANGPTL2 and diabetic foot ulcers (DFUs) are available. Here, we explored the potential link between ANGPTL2 and DFUs. Methods A total of 68 participants with type 2 diabetes mellitus (T2DM) were recruited, including 28 patients with DFU and 40 diabetic patients without DFUs. The clinical characteristics of T2DM patients with and without DFUs were compared. Serum concentrations of ANGPTL2 and VEGF were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANGPTL2 and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANGPTL2 and the severity and presence of DFUs. Results Serum levels of ANGPTL2 were higher in patients with DFUs than those in diabetic controls. Serum ANGPTL2 levels were higher in the advanced stages of DFUs. Spearman correlation analysis revealed strong positive associations of ANGPTL2 with CRP, VEGF and ESR in all subjects. In addition, serum ANGPTL2 was still positively correlated with DFUs stage after adjusting the risk factors. After adjusting for age, sex, HbA1C and duration of diabetes, ANGPTL2 was found to be independently associated with the presence of DFUs. Conclusions Circulating ANGPTL2 levels are an independent risk factor for DFUs. This suggests that ANGPTL2 may play important roles in the development of DFUs, a possibility that needs to investigated in prospective studies.


2021 ◽  
Vol 1 ◽  
pp. 97-101
Author(s):  
Faiq Gorial ◽  
Samaa Ezat ◽  
Mahmood Raheem Mahmood

Background: Rheumatoid arthritis is the most common cause of inflammatory polyarthritis. Interleukin‐37 (IL-37) has been found to play an important regulatory role in the development of inflammatory diseases. Objectives: To assess serum IL-37 level in rheumatoid arthritis (RA) patients compared to controls, to evaluate its diagnostic and predictive utility in RA patients and to investigate IL-37 level correlation with demographic and clinical characteristics of RA. Methods: Eighty subjects, 40 RA patients aged between 23-63 years and 40 healthy controls aged between 28-67 years were evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum IL-37 levels. Results: Serum IL-37 was significantly higher in RA patients compared to healthy controls. At optimum cut off value of >58.275 pg/ml, serum IL-37 had 100% accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. Serum IL‐37 level was not significantly related to Disease Activity Score of 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), also not correlated with C-reactive protein(CRP), rheumatoid factor(RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP). Also there was no correlation between the level of IL-37 and treatment. Conclusions: IL-37 was significantly higher in RA patients compared to healthy controls with a high diagnostic and predictive ability, and may be a potential biomarker for diagnosis and prediction of RA.


2021 ◽  
Author(s):  
Mingming Deng ◽  
Yan Yin ◽  
Qin Zhang ◽  
Xiaoming Zhou ◽  
Ting Yang ◽  
...  

Abstract Background & aimsImpaired exercise tolerance is a clinical feature of chronic obstructive pulmonary disease (COPD) associated with disease progression and increased mortality. The 6-minute walk test (6MWT) is a reliable and widely used measure of exercise capacity. However, it is not commonly used in primary medical institutions because it requires a suitable venue and professional training. Developing a simple tool to assess exercise tolerance is important. Molecular biomarkers show potential for evaluating the clinical outcomes (mortality, exacerbation) of COPD patients. The aim of this study was to identify simple and effective biomarkers to predict poor exercise tolerance in COPD patients.MethodsTen genes were selected by weighted correlation network analysis and differentially expressed gene analysis. Validation in an independent dataset led to the identification of PLA2G7, which was verified as a potential biomarker in COPD by bioinformatics analysis. The concentration of lipoprotein-associated phospholipase A2 (Lp-PLA2), which is encoded by the PLA2G7 gene, was assessed by enzyme-linked immunosorbent assay in a prospective validation cohort. The predictive capacity of Lp-PLA2 for 6-minute walk distance (6MWD) < 350 m was assessed using the area under the receiver operating characteristic curve (AUC). Traditional clinical features and Lp-PLA2 levels were incorporated into a nomogram to build a predictive model for poor exercise tolerance.ResultsThe final cohort included 92 stable COPD patients and 16 healthy smokers. Lp-PLA2 was upregulated in COPD patients and increased along with GOLD stage. Lp-PLA2 level was significant correlated with FEV1/FVC, BMI, FFMI, CAT score, mMRC score, and 6MWD in COPD patients. The predictive efficacy of Lp-PLA2 level (AUC: 0.796) and the derived nomogram model (AUC: 0.884) for exercise tolerance was superior to that of the sit-to-stand test and traditional clinical features.ConclusionLp-PLA2 is a promising biomarker for COPD patients and is suitable for assessing exercise tolerance in clinical practice.


2021 ◽  
Vol 8 ◽  
Author(s):  
Bi Huang ◽  
Li Tian ◽  
Zhaoran Chen ◽  
Liang Zhang ◽  
Wenjun Su ◽  
...  

Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to find the potential AAD biomarkers using a transcriptomic strategy. Arrays based genome-wide gene expression profiling were performed using ascending aortic tissues which were collected from AAD patients and healthy donors. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR) and western blot. The plasma levels of a potential biomarker, angiopoietin 2 (ANGPT2) were determined in case-control cohort (77 AAD patients and 82 healthy controls) by enzyme linked immunosorbent assay. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic power of ANGPT2 for AAD. Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (foldchange&gt;3.0, p &lt; 0.01). By bioinformatic analysis, we identified ANGPT2 as a candidate biomarker for blood-based detection of AAD. The qRT-PCR and protein expression demonstrated that ANGPT2 increased 2.4- and 4.2 folds, respectively in aortic tissue of AAD patients. Immunohistochemical staining demonstrated that ANGPT2 was markedly increased in intima of the aortic wall in AAD. Furthermore, ANGPT2 was significantly elevated in AAD patients as compared with controls (median 1625 vs. 383 pg/ml, p &lt; 1E-6). ROC curve analysis showed that ANGPT2 was highly predictive of a diagnosis of type A AAD (area under curve 0.93, p &lt; 1E-6). Sensitivity and specificity were 81 and 90%, respectively at the cutoff value of 833 pg/ml. In conclusion, ANGPT2 could be a promising biomarker for diagnosis of AAD; however, more studies are still needed to verify its specificity in diagnosing of AAD.


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