Eosinophil Cationic Protein Levels Research Articles

A rat model of adenoid hypertrophy constructed by using ovalbumin and lipopolysaccharides to induce allergy, chronic inflammation, and chronic intermittent hypoxia.

Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH. An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-β were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated. Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-β levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement. The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.

Chronic Rhinosinusitis With Nasal Polyps Does Not Affect the Association Between the Nasal Provocation Test and Serum Allergen-Specific Immunoglobulin E Levels

Background and Objectives: This study compared nasal provocation test (NPT) results between groups with and without chronic rhinosinusitis with nasal polyps (CRSwNP) to investigate whether CRSwNP affects the response to the intranasal allergen challenge.Methods: We reviewed the medical records of patients who had undergone the NPT, multiple allergen simultaneous test (MAST), and paranasal sinus computed tomography. Patients were diagnosed with CRSwNP based on findings from nasal endoscopy and paranasal sinus computed tomography. The NPT for house dust mites was conducted, and a positive MAST diagnosis was determined when the levels of immunoglobulin E specific to <i>Dermatophagoides farinae</i> and <i>Dermatophagoides pteronyssinus</i> were equal to or greater than 2 positives or at least 0.70 IU/mL. We statistically analyzed the NPT results and their correlation with MAST outcomes, comparing the CRSwNP group to the non-CRSwNP group.Results: Out of 99 participants, 30 had CRSwNP and 69 did not. There were no significant differences between the groups regarding MAST positivity, eosinophil count, eosinophil cationic protein levels, or responses to intranasal house dust mite challenges. The presence of CRSwNP did not significantly influence the correlation between NPT outcomes and MAST results.Conclusion: The presence of CRSwNP did not influence the outcomes of the NPT or its correlation with the results of the MAST. Additional large-scale, longitudinal studies are warranted to validate these findings.

Mechanisms of Er Chen Tang on Treating Asthma Explored by Network Pharmacology and Experimental Verification.

The aim of this study is to explore the active ingredients of ECT and their targets for asthma and investigate the potential mechanism of ECT on asthma. Firstly, the active ingredients and target of ECT were screened for BATMAN and TCMSP, and functional analysis was done via DAVID. Then, the animal model was induced by ovalbumin (OVA) and aluminum hydroxide. Eosinophil (EOS) counts, EOS active substance Eosinophilic cationic protein (ECP) and eotaxin levels were detected following the instruction. Pathological changes in lung tissue were examined by H&E staining and transmission electron microscopy. Interleukin (IL-4, IL-10, IL-13, TNF-α), TIgE and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Finally, the protein expression of the TGF-β / STAT3 pathway to lung tissue was detected by Western Blot. A total of 450 compounds and 526 target genes were retrieved in Er Chen Tang. Functional analysis indicated that its treatment of asthma was associated with inflammatory factors and fibrosis. In the animal experiment, the results showed that ECT significantly regulated inflammatory cytokine (IL-4, IL-10, IL-13, TNF-α) levels in (P<0.05, P<0.01, reduced EOS number (P<0.05) and also ECP and Eotaxin levels in the blood (P<0.05) in BALF and/or plasma. Bronchial tissue injury was obviously improved on ECT treatment. Associated proteins in TGF-β / STAT3 pathway were significantly regulated by ECT (P<0.05). This study originally provided evidence that the Er Chen Tang was effective in the treatment of asthma symptoms, and its underlying mechanism might be the regulation of inflammatory factor secretion and the TGF-β/STAT3 signaling pathway.

Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 μg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 μg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels &gt;17.0 μg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

Serum Eosinophilic Cationic Protein as a Useful Noninvasive Marker of Eosinophilic Gastrointestinal Disease in Children.

Recently, the prevalence of eosinophilic gastrointestinal disease (EGID) has shown an increasing trend worldwide. As the diagnosis of EGID requires invasive endoscopy with biopsy, noninvasive markers for detecting EGID in suspected patients, particularly children, are urgently needed. Therefore, this study aimed to evaluate the diagnostic accuracy of serum eosinophil cationic protein (ECP) beyond peripheral eosinophil counts in pediatric patients with EGID. Overall, 156 children diagnosed with EGID were enrolled and 150 children with functional abdominal pain disorder (FAPD) were recruited as controls. All participants underwent endoscopic biopsy in each segment of the gastrointestinal (GI) tract and serum ECP measurement, as well as peripheral eosinophil percent and absolute eosinophil count. Comparing EGID (n=156) with FAPD (n=150) patients, serum ECP levels were significantly higher in pediatric patients with EGID than in those with FAPD (25.8±28.6 µg/L vs. 19.5±21.0 µg/L, p=0.007), while there was no significant difference in peripheral eosinophil percent and absolute eosinophil counts between the two groups. Serum ECP levels were correlated with peripheral eosinophil percent (r=0.593, p<0.001) and the absolute eosinophil count (r=0.660, p<0.001). The optimal cutoff value of serum ECP for pediatric EGID was 10.5 µg/mL, with a sensitivity of 69.9% and a specificity of 43.4% with an area under the receiver operating characteristic curve of 0.562. The combination of serum ECP levels and peripheral eosinophil counts, when employed with appropriated thresholds, could serve as a valuable noninvasive biomarker to distinguish between EGID and FAPD in pediatric patients manifesting GI symptoms.

Role of peripheral and tissue eosinophils and eosinophil cationic protein in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.

The Efficacy of Budesonide, Levocabastine, and Their Combination in Treatment of Vasomotor Rhinitis

Introduction: Relevant studies have demonstrated that glucocorticoids and antihistamines, such as budesonide and azelastine, are effective in the treatment of vasomotor rhinitis, with their combined use being more effective than that of a single drug. The aim of this study was to assess the improvement in the symptoms of patients following the combined administration of these drugs. Methods: We conducted a single-center randomized study on 42 patients. Participants were randomly treated with budesonide, levocabastine hydrochloride, or their combination for 2 weeks. The visual analog scale (VAS) score and levels of eosinophil cationic protein (ECP), histamine (HA), leukotriene B4 (LTB4), and vasoactive intestinal peptide (VIP) in nasal secretions were evaluated before and after treatment. Results: The symptoms of patients were improved in all 3 treatment groups compared with those before treatment. Following combined treatment, the improvement in symptoms of nasal obstruction, runny nose, nasal itching, and sneezing was much greater than those in the groups treated with budesonide or levocabastine hydrochloride alone (p = 0.04, 0.004, 0.005, 0.004, respectively). The decreased levels of these inflammatory mediators were significantly different between the different treatment groups. Conclusions: Budesonide or levocabastine hydrochloride alone improved the nasal symptoms of patients with vasomotor rhinitis and reduced the levels of ECP, HA, LTB4, and VIP in nasal secretions. However, their combination improved the symptoms of patients more significantly than each drug alone.

Neuroinflammation as a Main Etiopathogenetic Factor in the Development of Drug-Resistant Epilepsies and Epileptic Encephalopathies

Background: despite the large number of newly emerging antiepileptic drugs, the frequency of treatment-resistant forms of epilepsy has not decreased, averaging 25–30%. Moreover the number of epileptic encephalopathies of early childhood has increased. One of the reasons of drug resistance is neuroinflammation. Aim: to evaluate the role of neuroinflammation in the pathogenesis of severe forms of childhood epilepsy and resistant adult epilepsy.Patients and methods: the main group 1 — 94 pediatric patients with epileptic encephalopathies, average age 20.4 ± 6.2 months. The control group 1 — 42 pediatric patients in remission of epilepsy, average age 21.3 ± 5.7 months. The main group 2 — 35 adult patients with resistant forms of epilepsy, average age 38.3 ± 7.9 years. The control group 2 — adult patients in remission of epilepsy 47 patients, average age 34.2 ± 8.6 years. The following blood levels were analyzed: neuron-specific enolase, S100 protein, eosinophilic cationic protein, IgE total level, total level of circulating immune complexes, leukocyte elastase and alpha-1 antitrypsin. Results: in the group of children with epileptic encephalopathies, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 27.6 ± 5.3 ng/ml compared to 14.2 ± 3.5 ng/ml in the control group. The average S100 protein level is 0.232 ± 0.041 ng/ml compared to 0.092 ± 0.024 ng/ml in the control group. The average level of eosinophilic cationic protein is 39.7 ± 9.4 ng/ml compared with 18.2 ± 5.3 ng/ml in the control group. The average IgE level is 157.3 ± 64.2 IU/ml compared to 42.2 ± 17.5 IU/ml in the control group. The average level of circulating immune complexes is 265.6 ± 54.4 UE/ml compared to 56.8 ± 16.8 UE/ml in the control group. In the group of adult patients with resistant forms of epilepsy, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 19.2 ± 7.2 ng/ml compared to 13.1 ± 4.1 ng/ml in the control group. The average S100 protein level is 0.115 ± 0.037 ng/ml compared to 0.093 ± 0.018 ng/ml in the control group. The average level of eosinophilic cationic protein is 24.2 ± 6.7 ng/ml compared to 18.8 ± 4.7 ng/ml in the control group. The average level of total IgE is 117.9 ± 32.6 IU/ml compared to 53.4 ± 18.2 IU/ml in the control group. The average level of circulating immune complexes is 235.2 ± 43.7 UE/ml compared to 62.6 ± 20.4 UE/ml in the control group. The level of leukocyte elastase was increased in 32 (91.4%) patients, the average level was 267.2 ± 36.8 nmol/min × ml compared with 175.2 ± 23.8 nmol/min × ml in the control group. The level of alpha-1 antitrypsin was increased in 33 (94.3%) patients, the average level was 55.2 ± 12.1 ng/ml compared with 26.4 ± 15.6 ng/ml in the control group. Conclusion: neuroinflammation is the factor of the development of severe forms of epilepsy and the formation of resistance in epileptic encephalopathies. Epileptic encephalopathies of early childhood according to their etiopathogenesis should be considered as subacute encephalitis, where seizures are only one sign of the pathological inflammatory process. The main clinical aim of the treatment of epileptic encephalopathies is the diagnosis of cumulative antigenic load and the selection of anti-inflammatory therapy.

Unraveling the complexities of drug reaction with eosinophilia and systemic symptoms (DRESS): Insights into clinical, laboratory, and histopathologic features of a case series from an Italian tertiary center

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially life-threatening drug hypersensitivity reaction. The diagnosis and management of DRESS are complicated due to its heterogeneous clinical and pathologic presentations, delayed onset of signs and symptoms, and unpredictable outcome. This retrospective study aimed to analyze cases of DRESS from a single Italian referring tertiary hospital center (Grande Ospedale Metropolitano Niguarda, Milan, Italy) with a focus on clinical features, causative drugs, histopathologic findings, and treatment. We have included 18 of 32 patients with a probable or definite diagnosis of DRESS. The study observed a slight predominance of women, with antimicrobials and allopurinol identified as the main causative drugs. Clinical manifestations varied, with a monomorphic maculopapular eruption being the most common, whereas facial edema and mucosal involvement were less frequently observed. Multiple organs were commonly affected, with liver and kidney involvement being prominent. Cardiac involvement was associated with the severity of eosinophilia. Laboratory evaluations showed elevated eosinophil levels and increased eosinophil cationic protein levels, supporting the role of eosinophils in DRESS pathogenesis. Histopathologic analysis revealed various patterns often coexisting in the same biopsy in 83% of cases, with interface dermatitis being the most frequent, followed by the perivascular pattern and the spongiotic/eczematous pattern. We observed eosinophils in the biopsy samples in about 50% of patients, and the relationship between peripheral eosinophilia and eosinophils in skin biopsies was not significant. In addition to the RegiSCAR score, age may play a role in predicting disease severity, as older patients with lower scores had poorer outcomes. The prognosis of DRESS depended on early identification, discontinuation of the causative agent, and appropriate therapy. Systemic corticosteroids were the primary treatment option.

Efficacy and Safety of Yukmijihwang-Tang in the Treatment of Cough-Variant Asthma: Study Protocol for a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Background: Cough-variant asthma (CVA), a precursor of typical asthma, is the main cause of chronic cough. We hypothesize that yukmijihwang-tang (YJT), which has been used for chronic cough in traditional medicine and has been reported to have an anti-inflammatory effect, could be an adjuvant to asthma treatment. Methods: We plan a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial to investigate the efficacy and safety of YJT in CVA patients. A total of 60 patients with CVA will be recruited and randomly assigned to either a high-dose YJT group, standard-dose YJT group, or control group (placebo) in a 1:1:1 allocation ratio after a 2-week run-in period. For the run-in period, only inhaled corticosteroids (ICSs) will be used, and the investigational drug will be administered once a day with concomitant ICS for 6 weeks. Data will be collected at baseline, week 3, and week 6, and the primary outcome measure will be the mean cough symptom score (CSS) change before and after medication. The secondary outcome measures will include the Leicester cough questionnaire-Korean version (LCQ-K) score, eosinophil count and eosinophil cationic protein level, pulmonary function test, and the number of uses of rescue medication, and so on. Conclusion: This study aimed to evaluate the efficacy and safety of YJT in concomitant treatment with ICS in patients with CVA and to determine the optimal dosage of YJT. The results are expected to provide evidence for the use of YJT as an adjuvant treatment for CVA.

The Correlation of Tissue’s Endotype Biomarkers and Dominant Inflammation Cell in Chronic Rhinosinusitis

Background and Objectives This study analyzes the relationship between endotype biomarkers and the type of tissue inflammation in chronic rhinosinusitis (CRS) in order to obtain a more accurate division of disease groups and appropriate therapy.Subjects and Method We carried out a cross-sectional study involving 33 samples of CRS patients. We conducted enzyme-linked immunosorbent assay to examine endotype biomarkers and histopathology methods to examine tissue inflammation.Results Statistical analysis with an independent t-test showed significant differences with respect to eosinophil cationic protein (ECP) between the eosinophilic and neutrophilic groups (p&lt;0.05), whereas there were no significant differences between the two groups (p&gt;0.05) with respect to Charcot-Leyden crystal (CLC), interleukin-5 (IL-5), interferon gamma (IFN-γ), interleukin- 17A (IL-17A), and oncostatin M (OSM). The Spearman test showed also showed that ECP, CLC, IL-5, IL-17A, IFN-γ and OSM had no significant correlation with the two groups (p&gt;0.05). The receiver operating characteristics analysis showed the optimal cut-off value of ECP of 342.22 pg/mL with sensitivity and specificity of 72.7% for determining the inflammation type (area under cover=0.78, p=0.009).Conclusion The higher level of ECP was more likely to be found in the eosinophilic tissue inflammation. Consequently, we propose using ECP as the main biomarker to identify the CRS type 2. Further research with a larger sample size is required for cut-off points of ECP in order to determine the endotype of CRS.

ANALYSIS OF THE RISK OF RECURRENT WHEEZING IN CHILDREN WITH BRONCHIOLITIS BASED ON THE WEIBULL MATHEMATICAL MODEL

Given the frequency of recurrent wheezing (up to 50 % of cases) in young children during the first year after bronchiolitis, the assessment of the prognostic value of diagnostic biological markers of bronchiolitis requires special attention.According to modern concepts, mast cells, eosinophils, play a significant role in the pathogenesis of bronchiolitis, with degranulation of which the release of cationic proteins (eosinophilic cationic protein (ECP), eosinophil-derived neurotoxin (EDN)) and molecular mediators, namely vascular cell adhesion molecule-1 (VCAM-1), which is a regulator of leukocyte adhesion and transendothelial migration. That is why VCAM-1, ECP and EDN are discussed as important prognostic markers in assessing the risk of recurrent wheezing in children with bronchiolitis.The aim of the study. To analyze the risk factors for recurrent wheezing in children with bronchiolitis, considering allergic history, the influence of external factors (passive smoking, place of residence), levels of VCAM-1, ECP, EDN in the blood serum.Material and Methods. This article is a part of the research work of the Department of Paediatrics No. 1 of Vinnytsia National Medical University named after M.I. Pyrohov on the topic "Optimization of diagnosis and treatment of somatic pathology in children", state registration No. 0115U007075.A clinical examination of 67 infants was carried out. The main group consisted of 34 children with bronchiolitis without a complicated allergic history. The comparison group consisted of 33 children with bronchiolitis who had a burdened allergic history. The average age of the children in the main group was 8.4±1.6 months, and 6.2±1.4 months in the comparison group. The analytical component of the study was based on parametric survival models (Weibull and generalized Gamma models). The analysis of Weibull models was performed in the statistical packages of analytical system R for Mac OS X FAQ, Version 3.1.0 2014-04-10, R. app 1.64 based on the Mac OS X 10.9 platform, 64-bit Intel Core i7 architecture.The study was approved by the Commission on Biomedical Ethics for compliance with the moral and legal rules for conducting medical research at Vinnytsia National Medical University named after M.I. Pyrohov. It was established that the research does not contradict the basic bioethical norms and meets the principles of compliance with the basic provisions of the GCP (1996), the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), WMA Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (1964-2008) and Order of the Ministry of Health of Ukraine No. 690 of 23.09.2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 of 12.07.2012). All patients were informed about the purpose and possible consequences of the research procedures. All patients signed an informed written consent to participate in the study prior to the procedure.Results of the study. The risks of recurrent wheezing in children with bronchiolitis according to the Weibull model were allergic history ( β=1,996) mixed feeding, and to an even greater extent artificial feeding ( β=7,832 and β=8,337). High serum levels of ECP β=5,03, EDN β=0,182 and VCAM-1 β=0,0254 are reliable markers of increased risk of recurrent wheezing in children with bronchiolitis. Living in rural areas ( β=-5,8) significantly reduces the risk of recurrent wheezing in children with bronchiolitis compared to children living in urban areas β=0.0162).Conclusions. 1. The levels of VCAM-1, ECP and EDN in the blood serum were recognized as reliable markers for the prognosis of recurrent vesicitis in children with bronchiolitis. The level of EDN ≤ 7 ng/ml in the blood serum is a prognostic marker for the risk of recurrent wheezing in children with bronchiolitis.2. The hypothesis that artificial feeding in children with bronchiolitis with a complicated allergic history confirms and significantly increases the risk of recurrent vesicitis in children with bronchiolitis. The hypothesis about the role of passive smoking exposure in a significant increase in the risk of recurrent wheezing in children with bronchiolitis was confirmed only for patients with EDN levels not exceeding 7 ng/ml in the blood serum.

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns.

Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.

Involvement of PAR2 in inflammatory mediator release from human blood eosinophils

Proteinase Activated Receptors (PARs) are the members of G-protein-coupled receptor family and can be cleaved by certain serine proteases to expose a tethered ligand domain, which binds and activates the receptors to initiate multiple signaling cascades. There is some evidence that certain proteases may regulate target cells by activating PARs. There are many studies, in which PARs play important roles in inflammation. One study indicated that PAR2 inhibition and deletion significantly suppressed the degree of inflammation due to decreased IL-6 and IL-1 levels. Another study also showed that PARs activation could mediate reactive oxygen species production and MAPK signaling leading to alveolar inflammation. In addition, platelet-derived CAPN1 can trigger the vascular inflammation associated with diabetes via cleavage of PAR1 and the release of TNF from the endothelial cell surface, and sarsasapogenin may alleviate diabetic nephropathy by the downregulation of PAR1. Another Phellodendron amurense bark extract can suppress the particulate matter-induced Ca2+ influx caused by direct action upon PAR2, alleviating inflammation and maintaining homeostatic levels of cell adhesion components. There are also other two antagonists of I-287 and GB88, which can reduce the PAR2-mediated inflammatory reaction. In this study, we tested expression of PARs and IL-5, IL-6, RANTES and ECP release from human blood eosinophils using different enzymes and PAR agonists. The expression of PARs was assessed in human blood eosinophils by flow cytometry and RT-PCR, and the levels of cytokine and eosinophil cationic protein (ECP) in the cultured supernatants were determined with ELISA kits. Flow cytometry shows that human eosinophils express PAR2 protein and do not express PAR1, PAR3 and PAR4 proteins. RT-PCR analysis revealed expression of PAR2 and PAR3 genes in human eosinophils. Tryptase, trypsin and elastase can induce significant IL-5, IL-6 and ECP release. Trypsin and elastase may also stimulate RANTES secretion, but tryptase cannot induce the RANTES secretion. Tryptase, trypsin and elastase-induced cytokine and ECP release from human blood eosinophils most likely occurs via activation of PAR2.

Correlating Salivary Levels of Immunoglobin E and Human Eosinophil Cationic Protein in the Aseer Cohort with Recurrent Apthous Stomatitis.

Repeated Aphthous Stomatitis (RAS) is the most prevalent inflammatory disorder of the oral mucosa, characterized by recurrent emergence of single or numerous painful ulcers. RAS usually affects healthy people without systemic illnesses.There is evidence linking atopy to the progression of this illness. Immunoglobulin E (IgE) and human eosinophil cationic protein (HECP) levels in the saliva of individuals with aphthous stomatitis were assessed as allergy-related indicators. Sixty people were assessed for this study. 30 patients with RAS were included in the patient group, while 30 healthy individuals made up for the control group. Sixty participants' non-stimulated saliva was taken and IgE and HECP were evaluated using enzyme-linked immunosorbent assay (ELISA). Data were analyzed in SPSS 20 through the Mann-Whitney test and p<0.05 was considered significant. The salivary level of HECP was significantly (p 0.05) higher among cases (0.83 0.70) compared to controls (0.170 0.15), whereas the salivary level of IgE was not significantly (p = 0.41) higher among cases (35.60 11.19) compared to controls (67.42 18.34). Even though this study found a positive correlation between elevated HECP levels and RAS, additional research with larger sample sizes is required to identify the biological mechanisms responsible for the observed associations and to include salivary HECP levels in the RAS patient's evaluation.

Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis.

Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis. Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4-/-, and Il13-/- mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-β receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries. Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.

Predictive Value of Eosinophil Cationic Protein in Nasal Secretions in Eosinophilic Chronic Rhinosinusitis.

To investigate the value of secretions Eosinophilic cationic protein (ECP) detection in the diagnosis of endotypes of Chronic rhinosinusitis (CRS) and its correlation with clinical symptoms, so as to provide guidance for the clinical application of EOS and ECP detection in secretions. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their EOS% and ECP levels were measured. Correlation analysis was performed for EOS% and ECP levels in secretions and tissues, respectively. The correlation between secretions EOS% and ECP and clinical symptom scores (symptomatic visual analog scale (VAS) scores, Lanza-kennedy scores from nasal endoscopy and Lund-Mackay scores from sinus CT) was further analyzed. Receiver operating characteristic curves were used to assess the predictive potential of EOS% and ECP in nasal secretions. Eosinophilic chronic rhinosinusitis (ECRS) patients had higher concentrations of ECP in nasal secretions than healthy subjects and NECRS (non-eosinophilic CRS) (p < 0.0001;0.0001); EOS% in nasal secretions was higher in ECRS than healthy subjects (p = 0.0055), but the differences between ECRS and NECRS were not statistically significant (p = 0.0999). Correlation analysis showed that tissue EOS% was correlated with ECP concentration and EOS% in nasal secretions (R = 0.5943;0.2815). There was a correlation between EOS% in secretions with a total LM score (R = 0.3131); ECP concentration in secretions with a total LK score (R = 0.3792). To diagnose ECRS, the highest area under the curve (0.8230) was determined for ECP in secretions; the highest area under the curve (0.6635) was determined for EOS% in secretions. Measurement of ECP in nasal secretions is useful for non-invasive diagnosis of ECRS. 3 Laryngoscope, 133:3304-3312, 2023.

Eosinophil Granule Proteins Involvement in Acute Appendicitis-An Allergic Disease?

Several pieces of evidence point to an allergic component as a trigger of acute appendicitis. As the Th2 immune response is characterized by eosinophil mobilization to the target organ and release of their cationic granule proteins, it is reasonable to investigate if the degranulation of eosinophils could be associated with the local injury. The primary aim of this study is to evaluate the participation of eosinophils granules proteins in acute appendicitis, both at local and systemic levels and the secondary aim is to evaluate the diagnostic accuracy of eosinophils granules proteins for the detection of acute appendicitis, as well as for distinguishing between complicated and uncomplicated acute appendicitis. Eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and eosinophil peroxidase (EP) are the most well-known eosinophil granule proteins. From August 2021 to April 2022, we present a prospective single-center study to evaluate the EDN, ECP, and EP concentrations simultaneously in appendicular lavage fluid (ALF) and the serum of 22 patients with acute phlegmonous appendicitis (APA), 24 with acute gangrenous appendicitis (AGA), and 14 normal controls. Concerning EDN, no differences were found between groups. ECP concentrations in ALF and serum were significantly higher in the histologically confirmed acute appendicitis compared to the control groups (p < 0.0001 and p < 0.0001, respectively). In ALF, no differences were found between ECP levels in APA: 38.85 ng/mL (IQR 26.50-51.77) and AGA 51.55 ng/mL (IQR 39.55-70.09) groups (p = 0.176). In the serum, no difference was found between ECP levels at APA: 39 ng/mL (IQR 21.30-56.90) and AGA: 51.30 ng/mL (IQR 20.25-62.59) (p = 0.100). For EP, the concentrations in ALF (p < 0.001) and serum (p < 0.001) were both higher in acute appendicitis compared to the control. In ALF, no difference was found between APA: 240.28 ng/mL (IQR 191.2-341.3) and AGA: 302.5 (IQR 227.7-535.85) (p = 0.236). In the serum, no differences were found between APA: 158.4 ng/mL (IQR 111.09-222.1) and AGA: 235.27 (IQR 192.33-262.51) (p = 0.179). Globally, the ALF concentrations were higher than serum concentrations, reflecting an intense inflammatory local reaction in AA. The optimal ECP cut-off for discriminating between acute appendicitis and the controls was >11.41 ng/mL, with a sensitivity of 93.5%, but with a specificity for identifying appendicitis of 21.4%, good discriminative power (AUC = 0.880). For EP, the optimal cut-off was >93.20 ng/mL, with a sensitivity of 87%, but with a specificity of 14.3% (AUC = 0.901), excellent discriminative power. For the diagnosis of perforated AA, the discriminative power of ECP and EP serum concentrations are weak (AUC = 0.562 and AUC = 0.664, respectively). Concerning the presence of peritonitis, the discriminative power of ECP and EP serum concentrations is acceptable, respectively: AUC = 0.724 and AUC = 0.735. Serum levels of EDN (p = 0.119), ECP (p = 0.586) and EP (p = 0.08) in complicated appendicitis were similar to uncomplicated appendicitis. Serum concentrations of ECP and EP can be added to decision-making AA diagnosis. A Th2-type immune response is present in AA. These data bring forward the role of an allergic reaction in the pathogenesis of acute appendicitis.

Diagnostic value of myeloperoxidase and eosinophil cationic protein in nasal secretions for endotypes of chronic rhinosinusitis.

To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.

A real life cohort of Mepolizumab treatment in severe eosinophilic asthma.

Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.