scholarly journals Calprotectin in rheumatic diseases

2016 ◽  
Vol 242 (8) ◽  
pp. 859-873 ◽  
Author(s):  
Francesca Ometto ◽  
Lara Friso ◽  
Davide Astorri ◽  
Costantino Botsios ◽  
Bernd Raffeiner ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Potential Role ◽  
Inflammatory Diseases ◽  
Disease Process ◽  
Serum Levels ◽  
Autoimmune Disorders ◽  
High Serum ◽  
Response To Treatment ◽  
Tnf Α ◽  
Activated Monocytes

Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker. Impact statement Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment.

The CX3C-Chemokine Fractalkine (CX3CL1) is Detectable in Serum of Patients Affected by the Inflammatory Diseases Allergic Rhinitis and/or Asthma

2005 ◽  
Vol 3 (3) ◽  
pp. 149-152
Author(s):  
P.L. Minciullo ◽  
M. Patafi ◽  
L. Giannetto ◽  
R.A. Merendino ◽  
G. Di Pasquale ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Potential Role ◽  
Inflammatory Diseases ◽  
Allergic Diseases ◽  
Serum Levels ◽  
Airway Disease ◽  
High Serum ◽  
Allergic Airway Disease ◽  
Inflammatory Conditions ◽  
Healthy Donors

Fractalkine (FKN) is a chemokine able to mediate the initial capture, firm adhesion, and activation of circulating leukocytes. Many tissues express FKN mRNA and FKN expression is increased during inflammatory conditions. To assess a possible involvement in allergic airway disease, we detected serum levels of FKN in a group of patients affected by allergic rhinitis and/or asthma and found high serum levels of FKN in all patients and in only 26% of healthy donors at lower concentrations. The present results underscore the potential role that this chemokine may play in the pathogenesis of respiratory allergic diseases.

Neuroendocrine system and chronic autoimmune rheumatic diseases

2013 ◽  
pp. 162-171
Author(s):  
Rainer H. Straub
Keyword(s):  
Nervous System ◽  
Rheumatic Diseases ◽  
Systemic Disease ◽  
Serum Levels ◽  
High Serum ◽  
Energy Regulation ◽  
Systemic Involvement ◽  
Autoimmune Rheumatic Diseases ◽  
Endocrine Disturbances ◽  
Fat Deposits

Endocrine abnormalities are very common in patients with chronic autoimmune rheumatic diseases (CARDs) due to the systemic involvement of the central nervous system and endocrine glands. In recent years, the response of the endocrine (and also neuronal) system to peripheral inflammation has been linked to overall energy regulation of the diseased body and bioenergetics of immune cells. In CARDs, hormonal and neuronal pathways are outstandingly important in partitioning energy-rich fuels from muscle, brain, and fat tissue to the activated immune system. Neuroendocrine regulation of fuel allocation has been positively selected as an adaptive programme for transient serious, albeit non-life-threatening, inflammatory episodes. In CARDs, mistakenly, the adaptive programmes are used again but for a much longer time leading to systemic disease sequelae with endocrine (and also neuronal) abnormalities. The major endocrine alterations are depicted in the following list: mild activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, inadequate secretion of ACTH and cortisol relative to inflammation, loss of androgens, inhibition of the hypothalamic-pituitary-gonadal axis and fertility problems, high serum levels of oestrogens relative to androgens, fat deposits adjacent to inflamed tissue, increase of serum prolactin, and hyperinsulinaemia (and the metabolic syndrome). Neuroendocrine abnormalities are demonstrated using this framework that can explain many CARD-related endocrine disturbances. This chapter gives an overview on pathophysiology of neuroendocrine alterations in the context of energy regulation.

scholarly journals An inflammatory cytokine signature helps predict COVID-19 severity and death

2020 ◽  
Author(s):  
Diane Marie Del Valle ◽  
Seunghee Kim-schulze ◽  
Huang Hsin-hui ◽  
Noam D Beckmann ◽  
Sharon Nirenberg ◽  
...  
Keyword(s):  
New York ◽  
Disease Severity ◽  
Cox Regression ◽  
Predictive Biomarkers ◽  
Clinical Information ◽  
Serum Levels ◽  
The United States ◽  
High Serum ◽  
Laboratory Test Results ◽  
Tnf Α

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

scholarly journals Circulating miRNA-125b Is a Potential Biomarker Predicting Response to Rituximab in Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Isabelle Duroux-Richard ◽  
Yves-Marie Pers ◽  
Sylvie Fabre ◽  
Meryem Ammari ◽  
Dominique Baeten ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Predictive Value ◽  
Predictive Biomarker ◽  
Serum Levels ◽  
High Serum ◽  
Response To Treatment ◽  
Serum Samples ◽  
Total Blood ◽  
Novel Mirna ◽  
Potential Biomarker

Although biologic therapies have changed the course of rheumatoid arthritis (RA), today’s major challenge remains to identify biomarkers to target treatments to selected patient groups. Circulating micro(mi)RNAs represent a novel class of molecular biomarkers whose expression is altered in RA. Our study aimed at quantifying miR-125b in blood and serum samples from RA patients, comparing healthy controls and patients with other forms of rheumatic diseases and arthritis, and evaluating its predictive value as biomarker for response to rituximab. Detectable levels of miR-125b were measured in total blood and serum samples and were significantly elevated in RA patients compared to osteoarthritic and healthy donors. The increase was however also found in patients with other forms of chronic inflammatory arthritis. Importantly, high serum levels of miR-125b at disease flare were associated with good clinical response to treatment with rituximab three months later (P=0.002). This predictive value was not limited to RA as it was also found in patients with B lymphomas. Our results identify circulating miR-125b as a novel miRNA over expressed in RA and suggest that serum level of miR-125b is potential predictive biomarker of response to rituximab treatment.

scholarly journals Two Patients with Extremely Elevated Tumor Markers: Where Is the Malignancy?

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Patrick P. J. van der Veek ◽  
Wouter H. de Vos tot Nederveen Cappel ◽  
Alexandra M. J. Langers ◽  
Bart van Hoek
Keyword(s):  
Tumor Markers ◽  
Malignant Disease ◽  
Elevated Serum ◽  
Serum Levels ◽  
Stone Disease ◽  
High Serum ◽  
Response To Treatment ◽  
Serum Tumor Markers ◽  
Painless Jaundice ◽  
Very High

Serum tumor markers are useful to evaluate a cancer's response to treatment, for early detection of cancer relapse, and, in some cases, to diagnose malignancy. In this paper, we present two patients with significantly elevated serum tumor markerswithoutevidence of malignant disease. An 18-year-old patient suffering from autoimmune hepatitis had markedly increased alpha-fetoprotein (aFP) levels (2,002 μg/L; normal <10 ug/L). Extensive imaging showed no signs of hepatocellular carcinoma or other cancer, and treatment with Prednisone led to rapid normalization of both liver enzymes and aFP. The second patient, a 60-year-old female with painless jaundice due to biliary stone disease, had very high serum levels of CA19-9 (18,000 kU/L, normal <27 kU/L). Liver biochemistry and serum CA19-9 concentration decreased to almost normal values (45 kU/L) after biliary stenting. These cases demonstrate that serum tumor markers can be elevated in benign disease and are therefore not appropriate to diagnose cancer.

High Serum Levels of CXCL11 in Mixed Cryoglobulinemia Are Associated with Increased Circulating Levels of Interferon-γ

2011 ◽  
Vol 38 (9) ◽  
pp. 1947-1952 ◽  
Author(s):  
ALESSANDRO ANTONELLI ◽  
CLODOVEO FERRI ◽  
SILVIA MARTINA FERRARI ◽  
ILARIA RUFFILLI ◽  
MICHELE COLACI ◽  
...  
Keyword(s):  
Strong Relationship ◽  
Serum Levels ◽  
Mixed Cryoglobulinemia ◽  
Interferon Γ ◽  
High Serum ◽  
Hepatitis C Infection ◽  
T Helper 1 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α

Objective.No study has evaluated circulating chemokine C-X-C motif ligand (CXCL)11 in patients with “mixed cryoglobulinemia and chronic hepatitis C infection” (MC+HCV). We measured CXCL11, and correlated this measurement to the clinical phenotype.Methods.Serum CXCL11, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were assayed in 97 MC+HCV patients and in 97 sex- and age-matched controls.Results.MC+HCV patients showed significantly higher mean CXCL11 serum levels than controls (254 ± 295, 68 ± 16 pg/ml, respectively; p = 0.0002; ANOVA). CXCL11 was significantly increased in 36 cryoglobulinemic patients with compared to those without active vasculitis (303 ± 208 vs 179 ± 62 pg/ml, respectively; p < 0.001; ANOVA). IFN-γ levels were significantly higher in MC+HCV than in controls [6.1 (range 0.8–114.5), 1.4 (range 0.7–2.4) pg/ml, respectively; p < 0.05; Mann-Whitney U test]. Serum TNF-α mean levels were significantly higher in MC+HCV than in controls [13.4 (range 1.8–369), 1.1 (range 0.7–3.2) pg/ml, respectively; p < 0.0001; Mann-Whitney U test]. A multiple regression analysis considering CXCL11 as a dependent variable, and age, alanine aminotransferase, IFN-γ, and TNF-α as independent variables, showed in MC+HCV patients a significant association only with IFN-γ (p < 0.0001).Conclusion.Our study demonstrates markedly high serum levels of CXCL11 in patients with MC+HCV compared to healthy controls overall in the presence of active vasculitis. A strong relationship between circulating IFN-γ and CXCL11 was shown, strongly supporting the role of a T helper 1 immune response in the pathogenesis of MC+HCV.

Prophylactic effect of aquatic extract of stevia on acetic acid induced-ulcerative colitis in male rats: a possible role of Nrf2 and PPARγ

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Abeer F. Mostafa ◽  
Mahmoud M. Elalfy ◽  
Ahmed Shata ◽  
Mona G. Elhadidy
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Inflammatory Diseases ◽  
Histopathological Examination ◽  
Antioxidant Properties ◽  
Thiobarbituric Acid ◽  
Serum Levels ◽  
Rectal Administration ◽  
Male Rats ◽  
Tnf Α

AbstractObjectivesUlcerative colitis (UC) is a non-specific intestinal inflammatory disease. Several studies demonstrated that inflammation and oxidative stress play significant role in the pathogenesis of this disease. This study aimed to determine the protective effect and possible mechanism by which stevia affects the course of experimentally induced colitis.MethodsMale rats were received stevia 20, 40, 80 mg/kg/day before induction of colitis by intra-rectal administration of 2 mL of 4% acetic acid, AA. Macroscopic and histopathological examination of the colon were done. Colonic content of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) activities and serum levels of interleukin (IL)1- β and tumor necrosis factor (TNF)-α were assessed. Real time-PCR (RT-PCR) was done to determine the expression of NF-κB, Nrf2 and PPARγ genes. Spontaneous contraction and effects of increasing concentrations of acetylcholine and stevia have been studied on the isolated colonic segments.ResultsStevia ameliorated colitis not only histopathologically but also it decreased the level of TNF-α, IL-1β, TBARS, MPO and the expression of NF-κB which were significantly increased in the AA group. The concentration of GSH, SOD, CAT and expression of Nrf2 and PPARγ were significantly increased with stevia. Moreover, stevia showed a relaxant effect on the colonic contractility which was increased in AA group. These all effects of stevia were more prominent with its highest dose.ConclusionOur results explored that, stevia acts protectively against UC by its anti-inflammatory and antioxidant properties which mediated by up-regulation of Nrf2 and PPARγ with downregulation of NF-κB. We suggest that stevia has the potential for treatment of chronic inflammatory diseases, such as UC.

Abstract P106: Polymorphisms in Candidate Genes and Early Atherosclerosis: A Study of 115 Autopsy Cases of Young Adults

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Débora S Faffe ◽  
Wiliam R Miranda ◽  
José B Netto ◽  
Fabiane S Lima ◽  
Leonardo Baumworcel ◽  
...  
Keyword(s):  
Young Adults ◽  
Complex Disease ◽  
Serum Levels ◽  
High Serum ◽  
Medical Institute ◽  
Nucleotide Polymorphisms ◽  
Promoter Polymorphisms ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
High Prevalence

Atherosclerosis, a major cause of death, is a complex disease, involving both genetic and environmental factors. Chronic inflammation plays a central role in its pathogenesis; however, the influence of genetic variations on early development of atherosclerosis has been poorly investigated. We examined the relationship of five common single-nucleotide polymorphisms (SNPs) with atherosclerotic severity in the anterior descendent coronary artery (DA) in 115 consecutive individuals under 30 years autopsied at the Legal Medical Institute of Rio de Janeiro. Histological sections were stained with hematoxilin-eosin and classified for atherosclerosis lesion accordingly to the American Heart Association. DNA was extracted and genotyped for SNPs in the angiotensin conversion enzyme, tumoral necrosis factor-alpha (−308G/A and −238 G/A), interferon-gama (+874 A/T), and metalloproteinase-9 (−1562 C/T) genes by automatic sequencing. Fire weapon lesion was the major causa mortis (72%). Population mean age was 26 years, 100 male and 15 female; 35% were slims, 58% regular weight and 7% obese; 22% white, 51% non-white, and 17% blacks. Only 2 subjects had normal DA histology, while 17 presented level II lesions, 74 level III, 7 level IV, 14 level V. and 1 level VI. 49 individuals presented genotype DD, related to high serum levels of ECA, while 18 were II (related with low ECA levels) and 48 DI (allele frequencies of D = 0,635; I = 0,365). For TNF-α promoter polymorphisms (where allele A is associated with high TNF-α level), 59 presented genotype GG, 21 GA, and 8 AA at position -308 (G = 0,790; A = 0,210), while 84 were GG, 3 GA, and 2 AA at position -238 (G = 0,961; A = 0,039). The allele T at position +874 of INF-γ (related to high INF-γ levels) was present in 45 subjects, while for MMP-9 SNP 49 individuals presented genotype CC, 14 CT, and 3 TT (C = 0,848; T = 0,152). In conclusion, we observed a high prevalence of early atherosclerotic lesions (level III) in young adults, with high prevalence of DD genotype, associated with high ECA serum levels.

scholarly journals Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients

2019 ◽  
Vol 9 (12) ◽  
pp. 332 ◽  
Author(s):  
Yasmeen M. Taalab ◽  
Wessam Fathi Mohammed ◽  
Manar A. Helmy ◽  
Alyaa A.A. Othman ◽  
Mohamed Darwish ◽  
...  
Keyword(s):  
Gene Expression ◽  
Serum Levels ◽  
High Serum ◽  
Cannabis Use ◽  
University Hospital ◽  
Mrna Levels ◽  
Tnf Α ◽  
Epileptic Patients ◽  
Inflammatory State ◽  
Factor Α

The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment. We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis. The “Epilepsy-only” patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the “Cannabis+Epilepsy” group (p = 0.0001). IL-10 showed significantly lower levels in the “Epilepsy-only” patients compared to the controls and “Cannabis+Epilepsy” (p = 0.0001). Cannabis use is prevalent among epilepsy patients. Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels. Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy.

High serum levels of TNF-α after its administration for isolation perfusion of the limb

Cytokine ◽  
1992 ◽  
Vol 4 (6) ◽  
pp. 585-591 ◽  
Author(s):  
Jean Gérain ◽  
Danielle Liénard ◽  
Patricia Ewalenko ◽  
Ferdy J. Lejeune
Keyword(s):  
Serum Levels ◽  
High Serum ◽  
Tnf Α
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