scholarly journals Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 498-507 ◽  
Author(s):  
Hilary M. DuBrock ◽  
Josanna M. Rodriguez-Lopez ◽  
Barbara L. LeVarge ◽  
Michael P. Curry ◽  
Paul A. VanderLaan ◽  
...  

Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case-control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) >240 dynes·s·cm−5. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme-linked immunosorbent assay. Continuous variables were compared using a Mann-Whitney U test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls (median MIF level [interquartile range] in systemic circulation: 46.68 ng/mL [32.31–76.04] vs. 31.19 ng/mL [26.92–42.17], P = 0.009; in pulmonary circulation: 49.59 ng/mL [35.90–108.80] vs. 37.78 [21.78–45.53], P = 0.002). In patients with POPH, MIF levels were positively correlated with PVR ( r = 0.58, P = 0.006) and inversely correlated with cardiac output ( r = −0.57, P = 0.007). MIF >60 ng/mL or tricuspid regurgitation gradient >50 mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.

2003 ◽  
Vol 10 (3) ◽  
pp. 417-422 ◽  
Author(s):  
Shin Kariya ◽  
Mitsuhiro Okano ◽  
Katsuya Aoji ◽  
Michiya Kosaka ◽  
Emiko Chikumoto ◽  
...  

ABSTRACT Otitis media with effusion (OME) is one of the most common ear diseases. Bacterial endotoxins and several inflammatory cytokines appear to be involved in the pathogenesis of OME in children; however, little is known of the immunological aspects of the onset of OME in adults. We sought to determine the presence of macrophage migration inhibitory factor (MIF) as well as interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), and endotoxin in middle ear effusions (MEEs) from adult patients with OME. In addition, the levels of MIF in MEEs from adults and children were compared. MEE was obtained from 95 adults and 11 children. The levels of MIF, IL-1β, TNF-α, and RANTES were determined by enzyme-linked immunosorbent assay, and the concentrations of endotoxin and total protein were determined by the Endospec assay and bicinchoninic acid assay, respectively. MIF was detected in 97.9% of the MEEs from adults, while endotoxin, IL-1β, TNF-α, and RANTES were detected in 96.8, 12.6, 5.3, and 43.9%, respectively. In addition, the level of MIF was significantly higher than those of endotoxin, IL-1β, and TNF-α. A positive correlation between the levels of MIF and endotoxin was observed. MIF and endotoxin were detected in 81.8 and 72.7%, respectively, of the MEEs from the children. The level of MIF was significantly higher in the children, and conversely that of endotoxin was significantly higher in the adults. These results suggest that the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults.


2021 ◽  
Vol 12 ◽  
Author(s):  
Maria S. Simon ◽  
Bianka Burger ◽  
Elif Weidinger ◽  
Gara Arteaga-Henríquez ◽  
Peter Zill ◽  
...  

Introduction: Previous research delivers strong indications that inflammatory activation leads to treatment resistance in a subgroup of patients with Major Depressive Disorder (MDD). Thus, tailored interventions are needed. The present study aimed to find potential biomarkers that may enable patients to be stratified according to immune activation.Methods: A phase IIa randomized placebo-controlled trial was performed to assess levels of inflammatory compounds in responders/remitters and non-responders/non-remitters to sertraline plus celecoxib (n = 20) and sertraline plus placebo (n = 23). Levels of macrophage migration inhibitory factor, neopterin, and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay; response and remission were measured by reduction of the Montgomery Åsberg Depression Rating Scale score.Results: Both treatment groups showed a significant decline in depression symptoms, but no difference was found between groups. A clear pattern emerged only for macrophage migration inhibitory factor: placebo remitters showed significantly lower baseline levels than non-remitters (a similar trend was seen in responders and non-responders) while celecoxib responders showed a trend for higher baseline levels than non-responders.Conclusion: Small subsample sizes are a notable limitation, wherefore results are preliminary. However, the present study provides novel insights by suggesting macrophage migration inhibitory factor as a promising biomarker for treatment choice.The trial was registered in EU Clinical Trials Register (EU-CTR): https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011990-34/DE, EudraCT-No.: 2009-011990-34.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Yveth Marlene Ortiz-García ◽  
Trinidad García-Iglesias ◽  
Gabriela Morales-Velazquez ◽  
Blanca Patricia Lazalde-Ramos ◽  
Guillermo Moisés Zúñiga-González ◽  
...  

Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dingcheng Shen ◽  
Caixi Tang ◽  
Shuai Zhu ◽  
Gengwen Huang

Abstract Background Various serum markers for early identification of severe acute pancreatitis (SAP) have been studied. Serum macrophage migration inhibitory factor (MIF) was reported to be correlated with severity of acute pancreatitis (AP) based on the 1992 Atlanta classification. However, MIF has never been proven to be predictive of disease severity based on the revised Atlanta classification (RAC). The potential predictive value of MIF needs to be further validated. Methods Consecutive patients with AP within 48 h after symptom onset and 10 healthy control volunteers were enrolled prospectively. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of MIF, clinical scores and other serum markers were determined. Results Among 143 patients with AP, there were 52 (36.4%), 65 (45.5%) and 26 (18.1%) with mild, moderate and severe disease based on the RAC respectively. Compared with healthy volunteers, serum levels of MIF were significantly higher in AP patients, especially those with SAP (P < 0.001). Multivariate regression analysis indicated that increased serum MIF (cut-off 2.30 ng/ml, OR = 3.16, P = 0.008), IL-6 (cut-off 46.8 pg/ml, OR = 1.21, P = 0.043), APACHE II score (cut-off 7.5, OR = 2.57, P = 0.011) and BISAP score (cut-off 1.5, OR = 1.01, P = 0.038) were independent risk factors for predicting SAP (P < 0.05). By using the area under the receiver operating characteristic (ROC) curve (AUC), MIF (AUC 0.950) demonstrated more excellent discriminative power for predicting SAP than APACHE II (AUC 0.899), BISAP (AUC 0.886), and IL-6 (AUC 0.826). Conclusions Serum MIF is a valuable early marker for predicting the severity of AP based on the RAC.


2021 ◽  
Author(s):  
Ji Sook Park ◽  
Jin Su Jun ◽  
Ji-Hyun Seo ◽  
Jae Young Lim ◽  
Chan-Hoo Park ◽  
...  

Abstract Objective: The study was to conduct an investigation of associated factor with macrophage migration inhibitory factor (MIF) in neonates.Results: MIF was measured by Enzyme-linked Immunosorbent Assay (ELISA) using sera obtained from sick neonates on the median postnatal 2.0nd day. Clinical details were reviewed from medical record and grouped into preterm and near or full-term neonates based on 34 weeks of gestation at birth. Statistical analyses were performed between MIF concentration and clinical factors. In total, 77 neonates consisted of preterm (n = 42) and term neonates (n = 35) were included. The median value of plasma MIF was higher in preterm neonates (7,037.6 pg/mL, IQR: 3,285.2-12,267.4) than in the others (3,968.8 pg/mL, IQR: 2,566.4-6,995.2, P = 0.013). Among 42 preterm neonates, those with necrotizing enterocolitis (NEC) in later had higher MIF concentration (12,170.9 pg/mL, IQR: 8,353.3-23,537.7, n = 9) compared with the others without NEC (5,189.6 pg/mL, IQR: 3,220.2-9,097.9, n = 33, P = 0.016). Associated factors of higher MIF in neonates were preterm neonates and NEC.


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