Association between specific IgE to staphylococcal enterotoxin B and the eosinophilic phenotype of asthma.

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.

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

OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Eosinófilos e proteína catiônica eosinofílica em bronquiolite viral aguda / Eosinophil counts and eosinophil cationic protein in acute viral bronchiolitis

Introdução: A bronquiolite viral aguda é uma doença freqüente na infância. Tem sido estudado o papel de marcadores imunológicos e inflamatórios como determinantes da sua gravidade. O objetivo deste estudo foi determinar a contagem de eosinófilos no sangue periférico e a concentração sérica de proteína catiônica eosinofílica em pacientes internados com bronquiolite viral aguda e comparar com diferentes graus de gravidade. Metodologia: A contagem de eosinófilos e a concentração da proteína catiônica eosinofílica foram determinadas em lactentes menores de 1 ano, hospitalizados com quadro clínico de bronquiolite. Foram realizadas comparações do número de eosinófilos e da concentração de proteína catiônica,de acordo com gravidade, sexo e faixa etária. Foram utilizados como critérios de gravidade a saturação em ar ambiente e a prevalência de ventilação mecânica. Resultados: Foram estudados 58 pacientes, com idade média de 2 meses. Dezenove pacientes foram classificados como graves, de acordo com a saturação da hemoglobina, inferior a 90%. Sete pacientes necessitaram ventilação mecânica (12%). A contagem de eosinófilos variou de 0 a 1104, com mediana de 100. O número de eosinófilos foi significativamente menor nos pacientes com saturação mais baixa (p<0.05). A concentração da proteína catiônica eosinofílica variou de 2 a 114 mg/litro, com mediana em 6 mg/l. Não houve correlação com a saturação. Conclusão: Houve associação entre baixo número de eosinófilos e gravidade da bronquiolite medida pela satHb. Estudos adicionais são necessários para elucidar melhor o papel de eosinófilos e seus derivados na determinação da gravidade da bronquiolite.

Introduction: The aim of the present study is to determine peripheral blood eosinophil counts and eosinophil cationic protein (ECP) serum concentration in hospitalized patients with acute viral bronchiolitis and to compare with different degrees of severity. Methodology: Peripheral blood eosinophil counts and eosinophil cationic protein serum concentration was performed on infants under 12 months of age who were hospitalized presenting acute viral bronchiolitis. Associations of eosinophil counts and ECP concentration among groups of patients were performed according to severity, gender and age.Severity was defined by haemoglobin saturation in room air and prevalence of mechanical ventilation. Results: Fifty-eight patients were studied. The mean age was 2 months. Nineteen patients were classified as severe according to haemoglobin saturation, lower than 90%. Seven patients needed mechanical ventilation (12%). Eosinophil counts ranged from 0 to 1104 and the median value was 100. Eosinophil counts were lower in patients with lower saturation (p<0.05). Patients who needed mechanical ventilation also showed lower eosinophil counts. ECP serum concentration ranged from 2 to 114 mg/land the median value was 6 mg/l. ECP was not associated with neither saturation nor mechanical ventilation. Conclusion: A correlation was found between eosinophil counts and severity measured by haemoglobin saturation. There was no correlation between ECP and severity. Additional studies are necessary to better explain the role of eosinophils and its proteins to determine the severity of bronchiolitis.

A distribuição dos eosinófilos nas diferentes fases de evolução do granuloma hepático em camundongos infectados pelo Schistosoma mansoni / Distribution of eosinophils at different stages of hepatic granuloma evolution in mice infected with Schistosoma mansoni

No presente estudo, avaliou-se a distribuição dos eosinófilos nas diferentes fases da formação do granuloma hepático de camundongos infectados pelo Schistosoma mansoni. A partir dos resultados obtidos sugerimos uma nova classificação para a evolução do granuloma hepático em camundongos montada a partir de fases descritas por outros autores. Em cada fase há um padrão diferente de distribuição dos eosinófilos. Na fase necrótico-exudativa os eosinófilos encontram-se concentrados na periferia e no centro do granuloma e na área de necrose eles são escassos; na "produtiva" os eosinófilos estão ainda distribuídos de maneira difusa por todo o granuloma; na de cura por fibrose se concentram na periferia e no centro do granuloma. Os eosinófilos estavam em contato direto com os ovos em todos os estágios de evolução dos granulomas. Conclui-se então que a dinâmica dos eosinófilos possui papel importante na formação da reação granulomatosa do hospedeiro e resolução do processo inflamatório causado pelo ovo do parasita, além de acrescentar novos dados na classificação dos granulomas hepáticos.

In the present study, the distribution of eosinophils at different stages of the formation of hepatic granuloma in mice infected with Schistosoma mansoni was evaluated. From the results obtained, we suggest a new classification for the evolution of hepatic granuloma in mice, constructed from the phases described by other authors. In each phase, there is a different pattern of eosinophil distribution. In the exudative-necrotic phase, the eosinophils are concentrated in the periphery and center of the granuloma, and are scarce in the necrotic area; in the productive phase, the eosinophils are dispersed throughout the granuloma; and in the cure due to fibrosis phase, the eosinophils are concentrated in the periphery and center of the granuloma. Eosinophils were found in direct contact with the eggs at all stages of evolution of the granuloma. It was concluded that the dynamics of eosinophils have an important role in forming the granulomatous reaction of the host and in resolving the inflammatory process caused by the parasite egg, as well as adding new data regarding hepatic granuloma classification.

Interrelationship between serum and sputum inflammatory mediators in chronic obstructive pulmonary disease

Little is known about airway inflammatory markers in chronic obstructive pulmonary disease (COPD). The objective of the present study was to identify and try to correlate pulmonary and peripheral blood inflammatory markers in COPD. In a cross-sectional study on patients with stable COPD, induced sputum and blood samples were collected for the determination of C-reactive protein, eosinophilic cationic protein, serum amyloid A protein, a-1 antitrypsin (a-1AT), and neutrophil elastase. Twenty-two patients were divided into two groups according to post-bronchodilator forced expiratory volume in the first second ( percentFEV1): group 1 (N = 12, FEV1 <40 percent) and group 2 (N = 10, FEV1 ³40 percent). An increase in serum elastase, eosinophilic cationic protein and a-1AT was observed in serum markers in both groups. Cytology revealed the same total number of cells in groups 1 and 2. There was a significantly higher number of neutrophils in group 1 compared to group 2 (P < 0.05). No difference in eosinophils or macrophages was observed between groups. Serum elastase was positively correlated with serum a-1AT (group 1, r = 0.81, P < 0.002 and group 2, r = 0.83, P < 0.17) and negatively correlated with FEV1 (r = -0.85, P < 0.03 and -0.14, P < 0.85, respectively). The results indicate the presence of chronic and persistent pulmonary inflammation in stable patients with COPD. Induced sputum permitted the demonstration of the existence of a subpopulation of cells in which neutrophils predominated. The serum concentration of all inflammatory markers did not correlate with the pulmonary functional impairment.

Níveis séricos de proteína catiônica eosinofílica e contagem de eosinófilos em crianças enteroparasitadas,residentes em área de baixo nível sócio-econômico na cidade de Natal, RN, Brasil / Serum eosinophil cationic protein levels end eosinophil counting in children enteroparasited

A Proteína Catiônica Eosinofílica (ECP) foi purificada de células humanas, pela primeira vez, em 1971 e, após cinco anos, foi identificada como sendo uma proteína granular eosinofílica que possui uma potente toxicidade para uma variedade de helmintos, bactérias e outros microrganismos. O objetivo deste trabalho foi diagnosticar as infecções por enteroparasitas correlacionando com níveis séricos de proteína catiônica eosinofílica e eosinofilia. Foram estudadas 150 crianças de ambos os sexos, com idade variando entre 3 e 6 anos, residentes no mesmo bairro e frequentadoras de creche. A Infecção Parasitária foi investigada por Exames de fezes pelosMétodos de Hoffmann, Pons & Janer e o de Baermann-Morais. Os níveis séricos de proteína catiônica eosinofílica foram determinadospor Fluoroenzimaimunoensaio, utilizando o Kit Unicap (Pharmacia & Upjonh) e a contagem de eosinófilos realizada em esfregaço sanguíneo corado pelo Leishman. Das crianças estudadas 140 (93,3%) apresentaram infecção por enteroparasitas e 10 (6,7%) apresentaram ausência de ovos e larvasde helmintos e cistos de protozoários. Cento e quarenta e oito amostras de soro foram analisadas para determinar os níveis de proteína catiônica eosinofílica e os resultados obtidos mostraram que foi 45,45μg/L a mediana das concentrações observadas e que com relação aos níveis de ECP em crianças parasitadas e não parasitadas por helmintos observou-se que as crianças parasitadas apresentaramconcentrações (MD=52,20μg/L) significantemente mais elevadas do que as não parasitadas (MD=29,70μg/L) e que houve uma correlação positiva entre níveis séricos de ECP e eosinófilos ( p< 0,0001 e r= 0,57).

The eosinophil cationic protein was purified from human cells, for the fist time in 1971, after five years, it was identified as being a eosinophil granular protein that is potencially toxic for helminthics, bacteria and other microorganisms. The purpose of this study was to diagnose the enteroparasitics infections co-related to the serum levels of eosinophil cationic protein and eosinophilia. One hundred and fifty children form both sexes, ages varying from 3 to 6 years old who live in the same neighbourhood and go to the same nursery were observed. The parasitic infection was investigated by faecal examinations using the Hoffmann, Pons & Janer and Baermann-morais methods. The serum cationic protein levels were determined by fluorimmunassay using the unicap kit (Pharmacia & Upjohn) and the counting of eosinophis was made by Leishman- stained smears. From the studied children 140 (93,3%) were infected by enteroparasitics and 10 (6,7%) showed no signs of eggs, helminthics, larva,and protozoarios cysts. One hundred and light samples of serum were analysed to determine the levels of eosinophil cationis protein and the obtaind results have showed that 45,45 ìg/L was the overage of the studied concentrations and that the relationship between the levels of eosinophil cationic protein (ECP) in parasited and non-parasited children was that the parasited children showed significantly hight concentrations (MD=52,20ìg/L) than the non-parasited children (MD=29,70 ìg/L). The results also have showed that there was a positive correlation between the serum levels of ECP and eosinophis ( p<0,0001 and r = 0,57).

Associação do polimorfismo do gene da proteína catiônica eosinofílica com a eosinofilia tecidual associada aos tumores em carcinomas espinocelulares de boca / Association of eosinophil cationic protein gene polymorphism with tumor-associated tissue eosinophilia in oral squamous cell carcinomas

A proteína catiônica eosinofílica (ECP) presente nos grânulos específicos dos eosinófilos apresenta atividade citotóxica, particularmente para células tumorais, entretanto a função exata dos eosinófilos e de seus produtos nas neoplasias malignas continua obscura. O objetivo desse trabalho foi investigar a prevalência do polimorfismo 434(G>C) do gene ECP em pacientes com carcinoma espinocelular (CEC) de boca e sua correlação com a eosinofilia tecidual associada aos tumores (TATE), bem como com as características demográficas, clínicas e microscópicas. O genótipo 434 do gene ECP em 165 pacientes saudáveis e em 157 pacientes com CEC de boca, tratados no Hospital do Câncer A. C. Camargo entre 1984 a 2002, foi detectado pela clivagem da seqüência específica de DNA amplificada com a enzima de restrição PstI e análise dos produtos de clivagem pela eletroforese em gel de agarose. A TATE foi determinada por análise morfométrica. A associação entre os genótipos, a intensidade da TATE e as variáveis demográficas, clínicas e microscópicas foi avaliada pelo teste qui-quadrado ou teste exato de Fisher. As análises das sobrevidas global, livre de doença e específica por câncer foram feitas pelo estimador limite de Kaplan-Meier e a comparação das curvas de sobrevida foi realizada utilizando-se o teste log-rank. Notou-se uma predominância dos indivíduos heterozigotos para o polimorfismo 434(G>C) do gene ECP. Nenhuma diferença estatística significativa foi obtida entre os diferentes genótipos, a intensidade da TATE e as variáveis demográficas, clínicas e microscópicas. Uma maior freqüência de esvaziamento cervical bilateral, recidiva local, embolização vascular, comprometimento das margens cirúrgicas e realização de radioterapia pós-operatória foi observada nos pacientes com CEC de boca, TATE intensa e genótipos 434GC/CC. Não houve correlação estatística significativa entre os diferentes genótipos 434 do gene ECP e as sobrevidas global, livre de doença e específica por câncer. Baseados em nossos resultados, concluímos que houve uma tendência de os pacientes com CEC de boca, intensa eosinofilia tecidual e genótipos 434GC/CC do gene ECP apresentarem uma evolução clínica desfavorável, quando comparados aos indivíduos com genótipo 434GG, provavelmente pela presença de uma variante genética dessa proteína com propriedades citotóxicas alteradas.

Eosinophil cationic protein (ECP), found in secretory granules of human eosinophils, presents cytotoxic activity, particularly against cancer cells. The specific functional role of eosinophils in solid malignant tumors remains unclear. The aim of this study was to investigate the prevalence of the ECP-gene polymorphism 434(G>C) in oral squamous cell carcinoma (OSCC) patients and its association with tumor-associated tissue eosinophilia (TATE), as well as demographic, clinical and microscopic variables. The 434 genotypes in the ECP-gene of 165 healthy individuals and 157 OSCC patients, submitted to surgical treatment at the Hospital A. C. Camargo from 1984 to 2002, were detected by cleavage of the amplified DNA sequence with restriction enzyme PstI and analyses of the cleaved product by agarose gel electrophoresis. TATE, in OSCC, was obtained by morphometric analysis. Chisquare test or Fisher’s exact test was used to analyze the association among ECP-gene polymorphism 434(G>C), TATE, demographic, clinical and microscopic variables. Diseasefree survival and overall survival were calculated by the Kaplan-Meier product-limit actuarial method and the comparison of the survival curves were performed using log rank test. Most of healthy individuals and OSCC patients showed the genotype 434GC. There was no statistical association among 434 genotypes, TATE intensity and demographic, clinical or microscopic variables of OSCC patients. Higher frequency of bilateral neck dissection, local recurrence, vascular embolization, involved resection margins and postoperative radiotherapy was detected in OSCC patients with intense TATE and 434GC/CC genotypes. No statistically significant differences on survival rates were found among 434 genotypes. In conclusion, these results suggest a tendency of worse clinical outcome in OSCC patients with intense TATE and 434GC/CC genotypes, probably due an ECP genetic variant with altered cytotoxic activity.

Atividade imuno-inflamatória de ovalbumina: papel de células e mediadores do sistema imune intestinal na migração de eosinófilos / Immuno-inflammatory activity of ovalbumin: role of the intestinal cells and immune mediators in the migration of eosinophils

Ratos são comumente usados em modelos de anafilaxia, principalmente em anafilaxia intestinal. Os mecanismos de hipersensibilidade são complexos e não estão completamente esclarecidos. Os objetivos deste estudo foram: a) investigar o efeito pró-inflamatório da ovalbumina no modelo de edema de pata em ratos sensibilizados; b) identificar os mediadores envolvidos nesta imuno-inflamação e, c) investigar o envolvimento de células do sistema imune intestinal e seus mediadores na fisiopatologia da hipersensibilidade intestinal induzida por ovalbumina (ova.). O edema de pata induzido por ova e sua modulação farmacológica foi estudada. Ratos Wistar previamente sensibilizados (14 a 18 dias) com ova (30mg, i.p.) ou pseudo-sensibilizados com hidróxido de alumínio (controle). Os volumes das patas foram mensurados antes dos estímulos antigênicos e 1, 2, 3 e 4 horas após a injeção intraplantar de ova (10 μg/pata). O pré-tratamento s.c. com dexametasona, difenidramina, ciproheptadina, clorpromazina, ou metisergida inibiram significativamente (p < 0,05) o edema de pata. NDGAm, indometacina, MK-886, WEB 2086, cetotifeno e meclizina não inibiram este edema. A talidomida e pentoxifilina foram ineficazes no controle do edema induzido por ovalbumina...