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1.
Korean J Intern Med ; 39(4): 659-667, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38986495

RESUMO

BACKGROUND/AIMS: Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics. METHODS: The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/µL) and serum specific IgE levels to 3 SAgs (0.35 kU/L). RESULTS: Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/clinfree IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all). CONCLUSION: These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.


Assuntos
Asma , Enterotoxinas , Eosinófilos , Imunoglobulina E , Fenótipo , Superantígenos , Humanos , Enterotoxinas/imunologia , Imunoglobulina E/sangue , Masculino , Asma/imunologia , Asma/sangue , Asma/diagnóstico , Feminino , Pessoa de Meia-Idade , Adulto , Eosinófilos/imunologia , Estudos de Casos e Controles , Superantígenos/imunologia , Superantígenos/sangue , Biomarcadores/sangue , Idoso , Eosinofilia/imunologia , Eosinofilia/sangue , Eosinofilia/diagnóstico , Proteína Catiônica de Eosinófilo/sangue , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/sangue , Neurotoxina Derivada de Eosinófilo/sangue
2.
J Immunol Methods ; 500: 113181, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34762913

RESUMO

Eosinophil-derived neurotoxin (EDN) is a surrogate biomarker of eosinophil activation and has considerable potential as a precision medicine biomarker in diseases where eosinophils may play a causative role. Clinical data for EDN have been generated using different quantitative immunoassays, but comparisons between these individual data sets are challenging as no internationally recognised EDN standards or orthogonal methods exist. In this study we aimed to compare commercial EDN assays from ALPCO, MBL, LSBio and CUSABIO for sample commutability. Firstly, we analytically validated the ALPCO enzyme linked immunosorbent assay (ELISA) and demonstrated appropriate analytical characteristics, including an intra/inter-assay precision coefficient-of-variation of between 1.9 and 6.8%. EDN purified from blood proved to be a good quality control material, whereas recombinant EDN, expressed in E.coli, did not react in the ALPCO immunoassay. Using healthy and asthma patient serum samples we confirmed that the ALPCO assay correlated well with the MBL assay, with a coefficient of determination (R2) of 0.92. However, the results from LSBio and CUSABIO assays were not commutable to the other assays.


Assuntos
Asma/diagnóstico , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos/imunologia , Humanos , Variações Dependentes do Observador , Controle de Qualidade , Reprodutibilidade dos Testes
3.
Thorax ; 77(6): 552-562, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615736

RESUMO

BACKGROUND: Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are proteins released by activated eosinophils whose role in adult asthma remains unclear. OBJECTIVE: To study associations between ECP, EDN and various asthma characteristics in adults from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). METHODS: Plasma ECP and EDN levels were measured by ELISA. Cross-sectional analyses were performed in 941 adults (43±16 years old, 39% with asthma) at EGEA2 (2003-2007). Longitudinal analyses investigated the associations between EDN level at EGEA2 and changes in asthma characteristics between EGEA2 and EGEA3 (2011-2013, n=817). We used generalised estimated equations adjusted for age, sex, smoking status and body mass index to take into account familial dependence. RESULTS: At EGEA2, both high ECP and EDN levels were associated with current asthma (adjusted OR (aOR) (95% CI): 1.69 (1.35-2.12) and 2.12 (1.76-2.57)). Among asthmatics, high EDN level was associated with asthma attacks (aOR: 1.50 (1.13-1.99)), wheezing and breathlessness (aOR: 1.38 (1.05-1.80)), use of asthma treatments (aOR: 1.91 (1.37-2.68)) and bronchial hyper-responsiveness (aOR: 2.03 (1.38-2.97)), even after further adjustment on ECP. High ECP level was associated with high neutrophil count and tended to be associated with chronic bronchitis. High EDN level at EGEA2 was associated with persistent asthma (aOR: 1.62 (1.04-2.52)), nocturnal symptoms (aOR from 2.19 to 3.57), worsening wheezing and breathlessness (aOR: 1.97 (1.36-2.85)) and nocturnal shortness of breath (aOR: 1.44 (1.04-1.98)) between EGEA2 and EGEA3. CONCLUSIONS: EDN and ECP were associated with different asthma expression in adults. EDN could be a potential biomarker to monitor asthma evolution in adults.


Assuntos
Asma , Proteína Catiônica de Eosinófilo , Neurotoxina Derivada de Eosinófilo , Adulto , Asma/diagnóstico , Proteínas Sanguíneas , Estudos Transversais , Dispneia , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos/metabolismo , Humanos , Pessoa de Meia-Idade , Sons Respiratórios
5.
Curr Opin Allergy Clin Immunol ; 20(1): 23-29, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31688152

RESUMO

PURPOSE OF REVIEW: The current understanding of eosinophilic chronic rhinosinusitis (CRS) has developed rapidly over the past decades. Classification of CRS based on the inflammatory endotype more accurately reflects the underlying pathophysiology and better directs treatment. Corticosteroids and more recently biologic agents, target the eosinophil inflammatory that drives this subtype of CRS. Tissue sampling is not always accessible or available and surrogate markers are sought to define this endotype of CRS. The purpose of this review is to assess current systemic predictors of eosinophilic CRS (eCRS) diagnosis. RECENT FINDINGS: Blood eosinophils are a moderate surrogate predictor of eCRS. A blood eosinophil count of more than 0.24 × 10/l predicts eCRS with tissue eosinophilia of more than 10 eosinophils per high-power field. It has been further shown that a blood eosinophil count more than 0.45 × 10/l is associated with need for long-term systemic therapy following endoscopic sinus surgery. Other biomarkers reviewed include IgE, eosinophilic cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, IL-5, periostin, eotaxin-3 and IL-16. SUMMARY: There remains limited data surrounding the prognostic use of biomarkers in eCRS. However, peripheral eosinophilia best predicts the eosinophilic density that best predicts the eCRS phenotype. In addition, it is also prognostic of need for more intensive therapy. Simple haematoxylin and eosin stained sinus mucosa still remains the most reliable tissue for assessment and is more accessible than bronchial biopsies.


Assuntos
Biomarcadores/sangue , Eosinófilos/patologia , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Doença Crônica , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Humanos , Imunoglobulina E/sangue
6.
J Asthma ; 57(11): 1211-1215, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31298976

RESUMO

Objective: Eosinophil-derived neurotoxin (EDN) is associated with recurrent wheezing episodes after bronchiolitis, childhood asthma, and allergic rhinitis. We investigated if there is a measurable difference between serum EDN levels in children with wheezing and non-wheezing respiratory infections.Methods: 171 children who visited a university hospital with respiratory infections were enrolled in the study. Subjects were divided into two groups: wheezing (n = 46) and non-wheezing (n = 125). Serum EDN levels were compared.Results: Serum EDN levels in the wheezing group were significantly higher than in the non-wheezing group (P < 0.001). The non-wheezing group was divided into three sub-groups: pneumonia, common cold, and tonsillitis. Serum EDN levels in the wheezing group were significantly higher than in the pneumonia, common cold, or tonsillitis subgroups (P < 0.001). There was no significant difference in serum EDN levels among the pneumonia, common cold, and tonsillitis subgroups.Conclusions: These findings suggest that elevated serum EDN levels could be a distinctive feature of respiratory infections with wheezing. EDN's utility as a biomarker for wheezing-associated disease should be explored through further study.


Assuntos
Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos/imunologia , Sons Respiratórios/diagnóstico , Infecções Respiratórias/diagnóstico , Biomarcadores/sangue , Criança , Pré-Escolar , Diagnóstico Diferencial , Neurotoxina Derivada de Eosinófilo/metabolismo , Eosinófilos/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Recidiva , Sons Respiratórios/imunologia , Infecções Respiratórias/sangue , Infecções Respiratórias/complicações , Infecções Respiratórias/imunologia
7.
Ital J Pediatr ; 45(1): 19, 2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696464

RESUMO

BACKGROUND: Clinically, asthma in children under 5 years old is under estimated because lack of diagnostic criteria. The current study was, therefore, designed to identify the predicting factors for recurrent wheezing in infants. METHODS: One hundred forty-five infants under 3-year old hospitalized with respiratory diseases were enrolled into this study. Patients were followed up for one-year period after being discharged from the hospital and were, then, divided into recurrent wheezing group and non-recurrent wheezing group based on whether there was recurrent wheezing or not. Wheezing or recurrent wheezing was specifically monitored in addition to blood tests for allergic and respiratory diseases. RESULTS: The prevalence of eczema and respiratory syncytial virus (RSV) infection were significantly higher in recurrent wheezing group than in control group (74.2% vs 45.8%; 32.3% vs. 13.3%, respectively, both P < 0.05); the percentage of blood eosinophil and serum eosinophil-derived neurotoxin (EDN) concentration at admission were also higher in recurrent wheezing group than in control group (3.10 ± 2.54% vs. 1.31 ± 1.15%; 68.67 ± 55.05 ng/mL vs. 27. 36 ± 19.51 ng/mL; respectively, both P < 0.001). Multivariate logistic regression analysis on eosinophil count and serum EDN concentration in predicting recurrent wheezing revealed that the eosinophil count showed the lowest sensitivity (51.6%) and highest specificity (90.4%), with the area under the ROC curve (AUC) of 0.752 ± 0.041; and that, in contrast, the serum EDN showed the highest sensitivity (88.7%) and lowest specificity (56.6%), with AUC of 0.795 ± 0.037. CONCLUSION: Combination of eosinophil count and serum EDN measurement may be better to predict the risk of recurrent wheezing in early life of childhood.


Assuntos
Sons Respiratórios/etiologia , Asma/epidemiologia , Estudos de Casos e Controles , Eczema/epidemiologia , Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos , Feminino , Humanos , Lactente , Contagem de Leucócitos , Masculino , Recidiva , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade
8.
J Infect Dis ; 219(9): 1474-1482, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30452713

RESUMO

BACKGROUND: Eosinophils are a prominent cell type in the host response to helminths, and some evidence suggests that neutrophils might also play a role. However, little is known about the activation status of these granulocytes during helminth infection. METHODS: We analyzed the expression of eosinophil and neutrophil activation markers in peripheral blood by flow cytometry and measured serum levels of eosinophil granule proteins in 300 subjects residing in an area endemic for soil-transmitted helminths (STH). The data generated are on samples before and after 1 year of 3-monthly albendazole treatment. RESULTS: Anthelmintic treatment significantly reduced the prevalence of STH. While eosinophil numbers were significantly higher in STH-infected compared to uninfected subjects and significantly decreased following albendazole treatment, there was no effect exerted by the helminths on either eosinophil nor neutrophil activation. Although at baseline eosinophil granule protein levels were not different between STH-infected and uninfected subjects, treatment significantly reduced the levels of eosinophil-derived neurotoxin (EDN) in those infected at baseline. CONCLUSIONS: These results show that besides decreasing eosinophil numbers, anthelmintic treatment does not significantly change the activation status of eosinophils, nor of neutrophils, and the only effect seen was a reduction in circulating levels of EDN. CLINICAL TRIALS REGISTRATION: http://www.isrctn.com/ISRCTN75636394.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Proteínas Granulares de Eosinófilos/sangue , Eosinófilos/metabolismo , Helmintíase/sangue , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Povo Asiático , Biomarcadores/sangue , Antígeno CD11b/metabolismo , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Proteína Catiônica de Eosinófilo/sangue , Proteína Básica Maior de Eosinófilos/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos/imunologia , Feminino , Proteínas Ligadas por GPI/metabolismo , Helmintíase/tratamento farmacológico , Helmintíase/imunologia , Humanos , Indonésia , Selectina L/metabolismo , Lectinas Tipo C/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Receptores de Complemento 3b/metabolismo , População Branca
9.
Dis Esophagus ; 31(2)2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29228243

RESUMO

Eosinophil peroxidase is an eosinophil-specific, cytoplasmic protein stored in the secondary granules of eosinophils. While eosinophil peroxidase deposition is increased in the esophagus in eosinophilic esophagitis (EOE), its potential role as a peripheral marker is unknown. This study aims to examine the relationship between serum eosinophil peroxidase and esophageal eosinophilia in eosinophilic esophagitis. Prospectively collected serum from 19 subjects with incident EoE prior to treatment and 20 non-EoE controls were tested for serum eosinophil peroxidase, eosinophilic cationic protein, and eosinophil derived neurotoxin using ELISA. Matching esophageal tissue sections were stained and assessed for eosinophil peroxidase deposition using a histopathologic scoring algorithm. Mean peripheral blood absolute eosinophil counts in eosinophilic esophagitis subjects were significantly elevated compared to controls (363 vs. 195 cells/µL, P = 0.008). Absolute median serum eosinophil peroxidase, eosinophil cationic protein, and eosinophil derived neurotoxin did not differ between groups; however, when normalized for absolute eosinophil counts, eosinophilic esophagitis subjects had significantly lower median eosinophil peroxidase levels (2.56 vs. 6.96 ng/mL per eos/µL, P = 0.002, AUC 0.79 (0.64, 0.94 95% CI)). Multivariate analysis demonstrated this relationship persisted after controlling for atopy. Esophageal biopsies from eosinophilic esophagitis subjects demonstrated marked eosinophil peroxidase deposition (median score 46 vs. 0, P < 0.0001). Normalized eosinophil peroxidase levels inversely correlated with esophageal eosinophil density (r = -0.41, P = 0.009). In contrast to marked tissue eosinophil degranulation, circulating eosinophils appear to retain their granule proteins in EoE. Investigations of normalized serum eosinophil peroxidase levels as a biomarker of EoE are ongoing.


Assuntos
Peroxidase de Eosinófilo/sangue , Eosinofilia , Esofagite Eosinofílica , Eosinófilos/patologia , Esôfago/patologia , Adulto , Idoso , Biomarcadores/sangue , Biópsia/métodos , Degranulação Celular , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Eosinofilia/sangue , Eosinofilia/etiologia , Esofagite Eosinofílica/sangue , Esofagite Eosinofílica/diagnóstico , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estatística como Assunto
10.
NPJ Prim Care Respir Med ; 27(1): 67, 2017 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-29255205

RESUMO

Allergic asthma is a chronic inflammatory disorder associated with elevated levels of immunoglobulin E (IgE), serum eosinophilic cationic protein (S-ECP), plasma eosinophil-derived neurotoxin (P-EDN) and fraction of exhaled nitric oxide (FENO). Poor self-rated health and sickness behaviour has repeatedly been associated with inflammatory markers, but the nature of this relationship in chronic inflammatory disease is not known. Likewise, such findings largely rely on cross-sectional investigations. Self-rated health (How would you rate your general state of health?), sickness behaviour (mean rating of satisfaction with energy, sleep, fitness, appetite and memory), IgE, S-ECP, P-EDN, and FENO were assessed in 181 non-smoking primary care patients with asthma in a 1-year longitudinal study. Associations between repeated measurements were calculated using mixed regression models and Spearman's correlations for change scores. Poor self-rated health was associated with high levels of seasonal IgE (p = 0.05) and food IgE (p = 0.04), but not total IgE or inflammatory markers. An increase over 1 year in perennial IgE was associated with a worsening of self-rated health (ρ = 0.16, p = 0.04). Poor self-rated health was associated with more pronounced sickness behaviour (p < 0.001), and a worsening in sickness behaviour was associated with a worsening of self-rated health over time (ρ = 0.21, p = 0.007). The study corroborates the importance of sickness behaviour as a determinant of self-rated health by showing that these factors co-vary over a 1-year period in a group of patients with allergic asthma. The importance of specific IgE for perceived health in primary care patients with mild to moderate asthma needs further investigation.


Assuntos
Asma/fisiopatologia , Nível de Saúde , Comportamento de Doença , Autorrelato , Adulto , Biomarcadores/sangue , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Expiração , Feminino , Humanos , Imunoglobulina E/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Adulto Jovem
11.
Ann Allergy Asthma Immunol ; 119(5): 441-445, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28866306

RESUMO

BACKGROUND: Eosinophils are encountered in many skin diseases, but the role of eosinophils in atopic dermatitis (AD) remains uncertain. OBJECTIVE: To examine the role of serum eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and total IgE as a biomarker of disease severity and relapse in severe recalcitrant AD. METHODS: We enrolled 99 patients with AD: 37 with severe recalcitrant AD, 20 with severe AD, and 42 with mild to moderate AD. We examined the difference in serum level of total IgE, ECP, and EDN between the groups and whether any correlation existed between disease severity and ECP or EDN. Lastly, difference in levels of ECP or EDN between those who experienced relapse was examined in the severe recalcitrant group. RESULTS: Serum levels of total IgE, ECP, and EDN were significantly higher in the severe recalcitrant AD group and severe AD group compared with the mild to moderate AD group. No significant difference was found in serum levels of total IgE, ECP, and EDN between the severe recalcitrant group and severe group. EDN had a significant positive correlation with the SCORing Atopic Dermatitis. No significant correlation was found between EDN and ECP. In the severe recalcitrant group, 29.7% of patients experienced relapse, and EDN was significantly higher in those who experienced relapse. The cutoff value of EDN for predicting relapse was 64.5. CONCLUSION: EDN correlated with the disease severity of AD. EDN may predict relapse in severe recalcitrant AD. The EDN serum level could be considered a candidate molecule as a clinical biomarker for evaluating AD disease activity and a predictor of relapse.


Assuntos
Biomarcadores/sangue , Dermatite Atópica/diagnóstico , Eczema/diagnóstico , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos/imunologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Prognóstico , Recidiva
12.
Sci Rep ; 7(1): 4833, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28684769

RESUMO

Bullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P < 0.01 and P < 0.05, respectively), whereas MBP values were lower (P < 0.001). ECP serum concentration decreased after 60 days of treatment in BP patients with ongoing remission but not in patients who later relapsed (P < 0.05). A reduction of at least 12.8 ng/mL in ECP concentrations provided a positive predictive value for remission of 81%, showing that ECP serum variation could be a useful biomarker stratifying BP patients at risk of relapse.


Assuntos
Anti-Inflamatórios/uso terapêutico , Clobetasol/uso terapêutico , Proteína Catiônica de Eosinófilo/genética , Eosinófilos/efeitos dos fármacos , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Movimento Celular/efeitos dos fármacos , Proteína Catiônica de Eosinófilo/sangue , Proteína Catiônica de Eosinófilo/imunologia , Proteína Básica Maior de Eosinófilos/sangue , Proteína Básica Maior de Eosinófilos/genética , Proteína Básica Maior de Eosinófilos/imunologia , Neurotoxina Derivada de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/genética , Neurotoxina Derivada de Eosinófilo/imunologia , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Expressão Gênica , Humanos , Masculino , Penfigoide Bolhoso/genética , Penfigoide Bolhoso/imunologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
13.
Allergol Int ; 66(1): 70-74, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27329145

RESUMO

BACKGROUND: This study was done to compare the efficacy of a recently developed eosinophil-derived neurotoxin (EDN) ELISA kit ("BioTracer™ K® EDN ELISA Kit") to a commercially available EDN ELISA kit ("MBL EDN ELISA Kit") and demonstrate the usefulness of serum EDN measurement in young asthmatic children. METHODS: Forty-eight children with physician-diagnosed asthma (Asthma group) and 31 age-matched normal controls (Control group) were recruited from the Asthma and Allergy Center at Inje University Sanggye Paik Hospital, Seoul, Korea from January 2010 to September of 2012. EDN levels in each serum specimen were measured 2 times using the: 1) BioTracer™ K® EDN ELISA Kit and 2) MBL EDN ELISA Kit at the Inje University Sanggye Paik Hospital laboratory. EDN level measurements in each serum specimen were compared. RESULTS: EDN measurements from the BioTracer™ K® EDN ELISA Kit correlated well with those from the MBL EDN ELISA Kit: r = 0.9472 at the Inje University Sanggye Paik Hospital laboratory. These r values were considered both clinically relevant (i.e., r > 0.85) and statistically significant (p < 0.0001). EDN measurements from both kits positively correlated with asthma symptom severity (p < 0.0001). No serious adverse events occurred during the study. CONCLUSIONS: The BioTracer™ K® EDN ELISA Kit was accurate and useful in measuring EDN levels in young asthma patient serum. Because of our kit's distinct advantages and utility, we suggest this kit can be used for the timely diagnosis, treatment, and monitoring of asthma in asthma patients of all ages, especially those too young to perform pulmonary function tests.


Assuntos
Asma/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Animais , Asma/diagnóstico , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lactente , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
J Clin Gastroenterol ; 51(2): 127-135, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27479142

RESUMO

BACKGROUND: The diagnosis and management of eosinophilic esophagitis (EoE) often requires multiple endoscopies. Serum biomarkers can be elevated in EoE patients, but their clinical utility in diagnosis and assessing response to treatment is not well established. GOALS: To evaluate serum biomarkers in EoE subjects compared with controls and assess longitudinally in response to treatment. STUDY: We conducted a prospective cohort study of children and adults undergoing esophagogastroduodenoscopy for suspected EoE. After completing an 8-week course of proton-pump inhibitor therapy, esophageal mucosal biopsies were obtained, as well as, serum analysis of absolute eosinophil count (AEC), eotaxin-3, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and interleukin-5. Subjects with normal endoscopic and histologic findings constituted controls. Those meeting criteria for EoE underwent repeat esophagogastroduodenoscopy and biomarker measurements following treatment with topical steroids for 8 weeks. RESULTS: Median levels of AEC (263.50 vs. 102 cu/mm, P<0.001), ECP (26.98 vs. 5.20 ng/mL, P<0.001) and EDN (31.70 vs. 14.18 ng/mL, P=0.004) were significantly elevated in EoE subjects compared with controls and correlated with esophageal eosinophilia. Levels of AEC (odds ratio, 1.79; 95% confidence interval, 1.28-2.64) and ECP (odds ratio, 1.61; 95% confidence interval, 1.23-2.36) were associated with a diagnosis of EoE. Among the 5 biomarkers evaluated, only AEC significantly predicted esophageal eosinophilia following topical steroid therapy in EoE subjects (P=0.006). CONCLUSIONS: AEC, ECP, and EDN were higher in EoE subjects compared with controls and correlated with degree of esophageal eosinophilia. Furthermore, AEC predicted post-treatment eosinophilia, suggesting a potential role in monitoring EoE disease activity.


Assuntos
Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Esofagite Eosinofílica/sangue , Esofagite Eosinofílica/tratamento farmacológico , Eosinófilos , Esteroides/administração & dosagem , Administração Tópica , Adolescente , Adulto , Biomarcadores/análise , Biópsia , Estudos de Casos e Controles , Criança , Pré-Escolar , Quimioterapia Combinada , Endoscopia do Sistema Digestório , Esofagite Eosinofílica/patologia , Mucosa Esofágica/patologia , Feminino , Humanos , Lactente , Contagem de Leucócitos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
15.
Scand J Gastroenterol ; 51(7): 835-41, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26854205

RESUMO

OBJECTIVE: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. METHODS: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. RESULTS: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups. CONCLUSION: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.


Assuntos
Colite Colagenosa/diagnóstico , Colonoscopia , Diarreia/diagnóstico , Proteínas Granulares de Eosinófilos/análise , Fezes/química , Hemorragia Gastrointestinal/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Doença Crônica , Proteína Catiônica de Eosinófilo/análise , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/análise , Neurotoxina Derivada de Eosinófilo/sangue , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Respir Med ; 111: 21-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26775606

RESUMO

BACKGROUND: Eosinophilic inflammation is frequently associated with increased asthma severity. Benralizumab is a humanized, afucosylated, anti-interleukin-5Rα monoclonal antibody that selectively depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To study effects of benralizumab on eosinophil counts and activity following administration to asthma patients. METHODS: Sera were collected from asthma patients enrolled in two clinical studies. Placebo or benralizumab was subcutaneously administered to patients in Phase I (100 or 200 mg, multiple doses; N = 14; NCT00659659) and Phase IIa (25, 100, or 200 mg every 4 weeks; N = 24; NCT00783289) studies. Sera were also collected from healthy volunteers (N = 20) for comparison. Blood eosinophils, IL-5, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eotaxin/chemokine (C-C motif) 11 (CCL11), eotaxin-2/CCL24, tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were measured at baseline and post-treatment. RESULTS: Increased EDN concentrations were observed in sera of patients from both studies relative to healthy volunteers (p < 0.05). At baseline, sera EDN concentrations correlated with blood eosinophil counts (rs = 0.5; p < 0.05). Benralizumab reduced blood eosinophil numbers and sera EDN and ECP relative to baseline (p < 0.05). No changes in TNF or IFN-γ were observed, while serum IL-5, eotaxin/CCL11, and eotaxin-2/CCL24 increased after benralizumab administration vs. placebo (p < 0.05). CONCLUSIONS: In two independent studies, serum IL-5, EDN, and ECP were modulated following benralizumab. Eosinophil depletion after benralizumab also resulted in significant reductions in EDN and ECP concentrations, suggesting that cytotoxic granule proteins were not released after eosinophil reduction.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/sangue , Asma/tratamento farmacológico , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Eosinófilos/efeitos dos fármacos , Adulto , Idoso , Citotoxicidade Celular Dependente de Anticorpos , Asma/imunologia , Biomarcadores/sangue , Método Duplo-Cego , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Humanos , Interleucina-5/sangue , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Allergy Asthma Proc ; 36(6): e113-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26534742

RESUMO

BACKGROUND: The serum level of eosinophil-derived neurotoxin (EDN), a protein present in eosinophil granules, correlates with the severity of childhood asthma. However, the relationship between the serum EDN level and the severity of adult asthma has not been sufficiently investigated. OBJECTIVE: This study aimed to elucidate the correlation between the serum EDN level and markers of severity in adult asthma. METHODS: The subjects comprised 83 adult patients who had asthma and who were undergoing treatment. Of these patients, 40 were positive for house-dust-specific immunoglobulin E (IgE) antibodies; 9 patients with severe adult asthma who were treated with omalizumab were included in the study. We measured the blood eosinophil count, serum EDN, and eosinophil cationic protein levels before investigating the correlations of these parameters with lung function and symptom score. RESULTS: There were no significant correlations between the blood eosinophil count or serum EDN or eosinophil cationic protein level with lung function and the symptom score in patients with asthma. However, serum EDN level was inversely correlated with the decrease percentage forced expiratory volume in 1 second (%FEV1) in patients positive for house-dust-specific IgE antibody (R = -0.54; p < 0.05), whereas no such correlation was observed in patients with negative results for house-dust-specific IgE antibody (R = 0.11; p = 0.468). A significant correlation was observed between a decrease in serum EDN level from baseline and lung function improvement after 8 weeks of omalizumab therapy (R = -0.77; p = 0.015). CONCLUSION: Serum EDN level may be a useful marker for monitoring persistent airflow limitation in adult patients with asthma who had positive results for house-dust-specific IgE antibodies.


Assuntos
Asma/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Animais , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/etiologia , Asma/fisiopatologia , Asma/terapia , Biomarcadores , Estudos Transversais , Proteína Catiônica de Eosinófilo/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Pyroglyphidae/imunologia , Testes de Função Respiratória , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Am J Gastroenterol ; 110(6): 821-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25781367

RESUMO

OBJECTIVES: Noninvasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE. METHODS: We conducted a prospective cohort study of consecutive adults undergoing outpatient esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded manner for interleukin (IL)-4, IL-5, IL-6, IL-9, IL-13, transforming growth factor (TGF)-α, TGF-ß, tumor necrosis factor-α, eotaxin-1, -2, and -3, thymic stromal lymphopoietin (TSLP), major basic protein, and eosinophil-derived neurotoxin. Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases. RESULTS: A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85 ± 160 vs. 43 ± 161 pg/ml (P=0.12) and 41 ± 159 vs. 21 ± 73 (P=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response. CONCLUSIONS: A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Esofagite Eosinofílica/sangue , Esôfago/patologia , Adulto , Idoso , Androstadienos/uso terapêutico , Budesonida/uso terapêutico , Estudos de Casos e Controles , Estudos de Coortes , Transtornos de Deglutição/sangue , Endoscopia do Sistema Digestório , Proteína Básica Maior de Eosinófilos/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/patologia , Feminino , Fluticasona , Refluxo Gastroesofágico/sangue , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Crescimento Transformadores/sangue
19.
PLoS One ; 8(6): e66644, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23805255

RESUMO

Aspirin-exacerbated respiratory disease (AERD) remains widely underdiagnosed in asthmatics, primarily due to insufficient awareness of the relationship between aspirin ingestion and asthma exacerbation. The identification of aspirin hypersensitivity is therefore essential to avoid serious aspirin complications. The goal of the study was to develop plasma biomarkers to predict AERD. We identified differentially expressed genes in peripheral blood mononuclear cells (PBMC) between subjects with AERD and those with aspirin-tolerant asthma (ATA). The genes were matched with the secreted protein database (http://spd.cbi.pku.edu.cn/) to select candidate proteins in the plasma. Plasma levels of the candidate proteins were then measured in AERD (n = 40) and ATA (n = 40) subjects using an enzyme-linked immunosorbent assay (ELISA). Target genes were validated as AERD biomarkers using an ROC curve analysis. From 175 differentially expressed genes (p-value <0.0001) that were queried to the secreted protein database, 11 secreted proteins were retrieved. The gene expression patterns were predicted as elevated for 7 genes and decreased for 4 genes in AERD as compared with ATA subjects. Among these genes, significantly higher levels of plasma eosinophil-derived neurotoxin (RNASE2) were observed in AERD as compared with ATA subjects (70(14.62∼311.92) µg/ml vs. 12(2.55∼272.84) µg/ml, p-value <0.0003). Based on the ROC curve analysis, the AUC was 0.74 (p-value = 0.0001, asymptotic 95% confidence interval [lower bound: 0.62, upper bound: 0.83]) with 95% sensitivity, 60% specificity, and a cut-off value of 27.15 µg/ml. Eosinophil-derived neurotoxin represents a novel biomarker to distinguish AERD from ATA.


Assuntos
Asma Induzida por Aspirina/diagnóstico , Biomarcadores/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Leucócitos Mononucleares/metabolismo , Adulto , Idoso , Área Sob a Curva , Asma Induzida por Aspirina/metabolismo , Asma Induzida por Aspirina/patologia , Estudos de Casos e Controles , Bases de Dados de Proteínas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade
20.
Biomarkers ; 18(3): 230-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23557131

RESUMO

OBJECTIVE: To determine whether eosinophil-derived neurotoxin (EDN) is a predictive marker of recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis. METHODS: EDN levels and recurrent wheezing episodes were serially measured in 200 infants hospitalized with RSV bronchiolitis. RESULTS: Serum EDN levels at 3 months correlated significantly with total wheezing episodes at 12 months in the RSV-PLC (n = 71; r = 0.720, p < 0.0001) and RSV-MONT groups (n = 79; r = 0.531, p < 0.001). Positive predictive value of 3-mo EDN level for total wheezing episodes was 57%; negative predictive value, 76%; sensitivity, 72%; specificity, 62%. CONCLUSION: EDN levels have predictive value for the development of recurrent wheezing post-RSV bronchiolitis.


Assuntos
Bronquiolite Viral/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Sons Respiratórios/diagnóstico , Infecções por Vírus Respiratório Sincicial/sangue , Vírus Sinciciais Respiratórios , Doença Aguda , Biomarcadores/sangue , Bronquiolite Viral/diagnóstico , Bronquiolite Viral/fisiopatologia , Bronquiolite Viral/virologia , Feminino , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Prognóstico , Recidiva , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Infecções por Vírus Respiratório Sincicial/virologia
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