Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis

2015 ◽  
Vol 47 (1) ◽  
pp. 177-185 ◽  
Author(s):  
Yael Gernez ◽  
Jeffrey Waters ◽  
Bojana Mirković ◽  
Gillian M. Lavelle ◽  
Colleen E. Dunn ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ex Vivo ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Basophil Activation Test ◽  
Surface Expression ◽  
Specific Ige ◽  
Basophil Activation ◽  
Cross Sectional ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

The diagnosis of cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) is clinically challenging, due to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between CF patients with and without ABPA.We conducted a prospective longitudinal study (Stanford cohort) comparing basophil activation test CD203c levels by flow cytometry before and after activation withAspergillus fumigatusallergen extract or recombinantAspf1 in 20 CF patients with ABPA (CF-ABPA) and in two comparison groups: CF patients withA. fumigatuscolonisation (AC) but without ABPA (CF-AC; n=13) and CF patients without either AC or ABPA (CF; n=12). Patients were tested every 6 months and when ill with pulmonary exacerbation. We also conducted cross-sectional validation in a separate patient set (Dublin cohort).Basophil CD203c surface expression reliably discriminated CF-ABPA from CF-AC and CF over time. Ex vivostimulation withA. fumigatusextract or recombinantAspf1 produced similar results within the Stanford (p<0.0001) and the Dublin cohorts. CF-ABPA patients were likelier to have elevated specific IgE toA. fumigatusand were less frequently co-infected withStaphylococcus aureus.Basophil CD203c upregulation is a suitable diagnostic and stable monitoring biomarker of ABPA in CF.

scholarly journals BASOPHILE ACTIVATION TEST FOR THE DIAGNOSTICS OF FUNGAL SENSITIZATION IN THE PATIENTS WITH CYSTIC FIBROSIS

2019 ◽  
Vol 21 (5) ◽  
pp. 919-928
Author(s):  
Ya. I. Kozlova ◽  
E. V. Frolova ◽  
A. E. Uchevatkina ◽  
L. V. Filippova ◽  
O. V. Aak ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Stimulation Index ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Basophil Activation Test ◽  
Specific Ige ◽  
Basophil Activation ◽  
Total Ige ◽  
Activation Test ◽  
Fungal Allergens ◽  
Fungal Sensitization

Aspergillus fumigatus colonization in the patients with cystic fibrosis (CF) may cause sensitization against A. fumigatus and/or allergic bronchopulmonary aspergillosis (ABPA), which significantly worsens the course of underlying disease. At the present time, new diagnostic tests are searched for detection of fungal sensitization in these patients. The aim of this work was to evaluate an opportunity of application of basophile activation test with A. fumigatus allergen in vitro using flow cytometry, aiming for identification of fungal sensitization in the CF patients. The study included 190 patients with CF aged 1 to 37 years. All the patients underwent common allergy screening (skin tests with fungal allergens, determination of serum levels of total IgE and specific IgE for the fungal allergens), and mycological examination (microscopy and culture of respiratory substrates). Computed tomography of the chest was performed upon clinical indications. The basophil activation test with the A. fumigatus allergen was performed in 10 CF patients with ABPA, and 10 CF patients without ABPA, in addition to the standard allergological examination. Frequency of sensitization to A. fumigatus in the patients with cystic fibrosis was 27%, the incidence of allergic bronchopulmonary aspergillosis was 5.7%. The number of eosinophils, total IgE and specific IgE levels in CF patients with ABPA were significantly higher than in CF patients without ABPA. In blood of the ABPA patients we have identified 68.5 (52.5-81.5%) of basophilic leukocytes activated by A. fumigatus allergen, with a stimulation index of 17.07 (10.30-27.70). In appropriate comparison group, the stimulation index did not exceed 1.5 (p = 0.000). Direct positive correlation between the levels of specific IgE to A. fumigatus and the number of basophils activated by A. fumigatus allergens was revealed (r = 0.77; р < 0.05). FVC values and the body mass index in CF patients with ABPA were significantly lower when compared with the patients without fungal sensitization. Introduction of the basophil activation test, along with standard techniques, may enable a more differentiated assessment of ABPA development in CF patients. Timely detection of associations between A. fumigatus sensitization and clinical status of CF patients will facilitate early and effective administration of specific therapy.

scholarly journals New opportunities in the diagnosis of asthma with sensitization to Aspergillus spp.

2021 ◽  
Vol 13 (2) ◽  
pp. 67-76
Author(s):  
Yana I. Kozlova ◽  
Alexandra E. Uchevatkina ◽  
Larisa V. Filippova ◽  
Oleg V. Aak ◽  
Valeriy D. Kuznetsov ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stimulation Index ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Basophil Activation Test ◽  
Study Groups ◽  
Specific Ige ◽  
Basophil Activation ◽  
Activation Test ◽  
Cellular Analysis ◽  
Index Value

BACKGROUND:Diagnosis of asthma with sensitization toAspergillusspp. is becoming increasingly important due to the severe, uncontrolled course of the disease and the possibility of the formation of allergic bronchopulmonary aspergillosis. AIM:To evaluate the possibility of using the basophil activation test using flow cytometry for the diagnosis of asthma with sensitization toAspergillusspp. MATERIALS AND METHODS:118 patients with asthma were examined. The levels of total IgE and specific IgE to aeroallergens were determined in the blood serum by the enzyme immunoassay. Basophil activation was studied by flow cytometry using the Allergenicity kit (Cellular Analysis of Allergy, Beckman-Coulter, USA). The allergenAspergillus fumigatus(Alcor Bio, Russia) was used to stimulate basophils. RESULTS:The first group consisted of 57 patients with asthma without sensitization toAspergillusspp. The second group included 36 patients with asthma with sensitization toAspergillusspp. The third group consisted of 25 patients with allergic bronchopulmonary aspergillosis. The number of basophils activated by theAspergillusfumigatusallergen in patients with asthma with sensitization toAspergillusspp. and allergic bronchopulmonary aspergillosis was significantly higher than in the asthma group and amounted to 8.1 [5.2; 20.9]% and 84.6 [75.7; 94.0]%, respectively (p 0.001). The stimulation index in the study groups ranged from 0.7 to 72.6. The optimal diagnostic point (cut off) for identifying patients with asthma withAspergillusspp. sensitization there was an stimulation index value of more than 2.4, and for patients with allergic bronchopulmonary aspergillosis 15.95. Among all patients with sensitization toAspergillusspp. a positive correlation was established between the level of specific IgE toAspergillusspp. and the percentage of basophils activated by the allergenAspergillusfumigatus(r= 0.792,p 0.001) and stimulation index (r= 0.796,p 0.05). CONCLUSIONS:The basophil activation test can be used as an additional diagnostic method for asthma with sensitization toAspergillusspp. and allergic bronchopulmonary aspergillosis.

scholarly journals Associations between Hypertension, Treatment, and Cognitive Function in the Irish Longitudinal Study on Ageing

2020 ◽  
Vol 9 (11) ◽  
pp. 3735
Author(s):  
Sook Ling Leong ◽  
Ian H. Robertson ◽  
Brian Lawlor ◽  
Sven Vanneste
Keyword(s):  
Longitudinal Study ◽  
Cognitive Function ◽  
Epidemiological Studies ◽  
Hypertension Treatment ◽  
Hypertension Status ◽  
Antihypertensive Medications ◽  
Cross Sectional ◽  
Prospective Longitudinal Study ◽  
Longitudinal Associations ◽  
Prospective Longitudinal

Epidemiological studies have produced conflicting results regarding the associations between the use of different hypertensive drugs and cognition. Data from the Irish Longitudinal Study on Ageing (TILDA), a nationwide prospective longitudinal study of adults aged 50 or more years, was used to explore the associations between hypertensive status, categories of antihypertensive and cognitive function controlling for age, education, and other demographic and lifestyle factors. The study sample included 8173 participants. ANCOVAs and multivariate regressions were used to assess the cross-sectional and longitudinal associations between cognitive function and hypertension status and the different categories of hypertensive medication. Hypertension was not associated with decline in global cognitive and executive functions and were fully explained by age and education. Different hypertensive medications were not associated with cognitive function. Consistent with previous studies, changes in cognition can largely be explained by age and education. The use of antihypertensive medications is neither harmful nor protective for cognition.

scholarly journals NPPA promoter hypomethylation predicts central obesity development: a prospective longitudinal study in Chinese adults

Obesity Facts ◽  
2021 ◽  
Author(s):  
Jing Li ◽  
Jinhua Zhu ◽  
Qiu Zhang ◽  
Linan Chen ◽  
Shengqi Ma ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Obesity ◽  
Molecular Mechanisms ◽  
Permutation Test ◽  
Chinese Adults ◽  
Cross Sectional ◽  
Prospective Longitudinal Study ◽  
Targeted Bisulfite Sequencing ◽  
Prospective Longitudinal

Introduction: Atrial natriuretic peptide (ANP) plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its coding gene (NPPA) methylation and obesity. Methods: Peripheral blood DNA methylation of NPPA promoter was quantified at baseline by targeted bisulfite sequencing for 2,497 community members (mean aged 53 years, 38% men) in the Gusu cohort. Obesity was repeatedly assessed by body mass index (BMI) and waist circumference (WC) at baseline and follow-up examinations. The cross-sectional, longitudinal, and prospective associations between NPPA promoter methylation and obesity were examined. Results: Of the 9 CpG loci assayed, DNA methylation levels at 6 CpGs were significantly lower in participants with central obesity than those without (all P<0.05 for permutation test). These CpG methylation levels at baseline were also inversely associated with dynamic changes in BMI or WC during follow-up (all P<0.05 for permutation test). After an average 4 years of follow-up, hypermethylation at the 6 CpGs (CpG2 located at Chr1: 11908348, CpG3 located at Chr1:11908299, CpG4 located at Chr1:11908200, CpG5 located at Chr1:11908182, CpG6 located at Chr1:11908178, and CpG8 located at Chr1:11908165) were significantly associated with a lower risk of incident central obesity (all P<0.05 for permutation test). Conclusions: Hypomethylation at NPPA promoter was associated with increased future risk of central obesity in Chinese adults. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of central obesity.

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