Summary
Background
Adverse systemic reactions (SRs) are more common in honeybee venom immunotherapy (VIT) than in wasp VIT. Factors that might be associated with SRs during the honeybee VIT are ...poorly understood.
Objective
Our aim was to evaluate risk factors for SRs during the build‐up phase of honeybee venom immunotherapy.
Methods
We included 93 patients who underwent ultra‐rush honeybee VIT. The adverse SRs and their severity was compared to various immunological (sIgE, tIgE, basophil CD63 response, baseline tryptase, and skin tests), patient‐specific (age, sex, cardiovascular conditions and medications, and other allergic diseases), and sting‐specific factors (anaphylaxis severity, time interval to onset of symptoms, and absence of cutaneous symptoms).
Results
Twenty‐three patients (24.7%) experienced mild SRs and 13 patients (14%) severe SRs. In five patients with severe SRs, the build‐up was stopped. High basophil allergen sensitivity, evaluated as dose–response curve metrics of EC15, EC50, CD‐sens, AUC, or the response to submaximal 0.01 μg/mL of venom concentration, was the most significant risk factor and only independent predictor of severe SRs and/or build‐up stop. Time interval of <5 min after sting to onset of symptoms and lower specific IgEs to rApi m1 was also associated with severe SRs. There was no difference in other immunological, patient‐specific, or sting‐specific factors, including the baseline tryptase. None of the studied factors was associated with mild SRs.
Conclusion and Clinical Relevance
High basophil allergen CD63 sensitivity phenotype was a major indicator of severe adverse SRs during the build‐up phase of honeybee VIT. Possibly role was also showed for short latency to filed sting reaction and low sIgE to rApi m1. Before honeybee VIT, measurement of basophil allergen sensitivity should be used to identify patients with a high risk for severe side‐effects.
Summary
Asthma is one of the most common chronic diseases in childhood. It is well known that genetic variability contributes to asthma risk. One of the most replicated asthma candidate genes is ...ORM1‐like 3 (Saccharomyces cerevisiae) (ORMDL3), which has been associated with childhood asthma susceptibility. Another asthma candidate gene is signal transducer and activator of transcription 6 (STAT6), a regulator of IgE class switching. Gene coding thromboxane A2 receptor (TBXA2R), involved in chronic airway inflammation, has been associated with asthma in several genetic studies. We have studied the association of polymorphism rs4795405 in ORMDL3, rs324011 in STAT6 as well as rs8113232 and rs3786989 in TBXA2R with asthma risk, various asthma phenotypes and asthma‐related symptoms. The study group consisted of 154 children with asthma, in whom clinical parameters were measured and whose asthma control and atopic status were determined. A control group comprised 71 healthy children. Genotyping was performed using an allelic discrimination assay. The ORMDL3 polymorphism rs4795405 was suggestively associated with asthma risk. Furthermore, it was significantly associated with nonatopic asthma and asthma without rhinitis. No association was detected between the STAT6 polymorphism rs324011 or the TBXA2R polymorphisms rs8113232 and rs3786989 and asthma susceptibility. However, an association between rs324011 in STAT6 with recurrent wheezing in early childhood and a suggestive association between rs8113232 in TBXA2R with rhinitis in children with asthma were observed. Our results confirmed ORMDL3 as a candidate gene for childhood asthma susceptibility. STAT6 and TBXA2R polymorphisms were not associated with asthma risk, but they were associated with asthma‐related symptoms.
The complement component C5a is a potent inflammatory peptide, which may be involved in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). We analysed the induced sputum and plasma of ...28 patients with stable COPD, 12 healthy smokers and 7 non-smokers. In 13 of the patients with COPD, we also observed paired samples during acute exacerbation. The concentrations of C5a/C5a desArg and C3a/C3a desArg were measured using cytometric bead array. Both C5a and C3a concentrations in induced sputum of stable patients with COPD were significantly increased compared to the control groups of healthy smokers and non-smokers. In addition, there was a significant elevation in C5a values in exacerbation of COPD that was independent from the airway C3a levels. Airway C5a levels were negatively correlated with forced expiratory volume in first second (FEV1)% predicted and diffusing capacity of the lung (TLCO). Plasma C5a concentrations in patients with COPD were significantly higher than in healthy smokers, but no further significant systemic C5a elevation was detected with acute exacerbation of COPD. There was no important difference in local or systemic C5a concentrations between healthy smokers and non-smokers. These in vivo results clearly show that local and systemic C5a concentrations in COPD are elevated, and that the local, in contrast to systemic, C5a concentrations additionally increase in the acute exacerbation of COPD. It seems that the cigarette smoke is not related to C5a increase. The elevated local and systemic C5a levels, and additional individual local C5a increase during the exacerbation support the importance of C5a in COPD.
There was no change in maximal basophil response when using allergen at concentrations of 5 and 50 mg/mL with median CD 63 expression over 70%.There was significant decreases in basophil response at ...sub-maximal birch pollen concentrations (0.5 mg/mL): 23.4% of CD63 positive basophils before SIT, 4.3% after 2 months and <4% after 5 months of SIT which correlated with reduction in symptoms.
Summary
Background
Airway angiogenesis may be an important part of structural remodelling in the pathogenesis of asthma. The development of asthma is frequently preceded by rhinitis.
Objective
We ...sought to determine whether the levels of angiogenesis‐related factors are elevated in airways of patients with rhinitis or controlled asthma.
Methods
We analysed the induced sputum of 18 rhinitis patients, 16 asthmatic patients, and 15 healthy controls. The concentrations of angiogenin, vascular endothelial growth factor (VEGF), IL‐8, fibroblast growth factor (bFGF), and TNF‐α were measured by cytometric bead arrays.
Results
We found significantly increased angiogenin and VEGF concentrations in the induced sputum supernatant of both rhinitis and asthma patients compared with that of the healthy control group (P0.0005). With the exception of TNF‐α, there was no difference in the other angiogenic factors; TNF‐α levels were higher in the rhinitis group than in the control group (P=0.02).
Conclusion
These in vivo results suggest increased airway angiogenesis in patients with rhinitis without asthma as well as in corticosteroid‐treated and well‐controlled asthma patients.
Early identification of methicillin-resistant Staphylococcus aureus (MRSA) carriers is a major component of an MRSA control programme. The cost and laboratory workload could be markedly reduced by ...processing multiple swabs from one person in one culture broth (specimen pooling). We evaluated the sensitivity for MRSA detection and the growth rate of pooled swabs compared with individual processing. In total, 1254 swabs from 423 subjects (two to five swabs per subject) were submitted for detection of MRSA. Swabs were suspended in 2-mL volumes of sterile Todd–Hewitt Broth and divided into two 1-mL aliquots. One aliquot of the suspension was processed as a single specimen, and the other aliquot was mixed (pooled) with other suspensions in which swabs from the same patient were suspended. Forty-four (10%) pooled samples were positive for MRSA. Specimens from seven additional patients that were negative when pooled were positive when processed separately. There was no case where the pooled specimen was positive but the separate specimens were negative. The diagnostic sensitivity of pooled surveillance cultures compared with single cultures, when only subjects colonized by MRSA were considered, was 86% and the false-negative rate was 14%. Eighty percent of the pooled positive cultures were detected by the third day and all were detected by the fourth day. Fifty-four percent of the specimens processed separately were detected by the second day and all were detected by the fourth day. Pooling of specimens decreases the sensitivity of MRSA detection compared with processing each swab separately, particularly in swabs with a low number of colony-forming units. In all subjects whose pooled samples were negative but whose swabs examined separately were positive, the swabs examined separately were negative on primary plates and positive only after culturing in enrichment broth.
Summary
Background
No study has assessed the diagnostic sensitivity of rApi m 1 and rVes v 5 on Immulite testing system.
Objective
To compare the diagnostic sensitivity of commercially available ...venom recombinant allergens between the currently available immunoassays ImmunoCAP (CAP) and Immulite (LITE) and establish their correlation with the severity of the sting reaction.
Methods
This study evaluated 95 bee venom and 110 yellow jacket venom‐allergic subjects. We measured the levels of sIgE to rApi m 1, rVes v 5 (LITE and CAP), rApi m 2 (LITE), rVes v 1 (CAP) and total IgE (CAP). Forty‐nine healthy subjects served as controls.
Results
The diagnostic sensitivity of rApi m 1 and rVes v 5 was significantly higher with the LITE than with the CAP system (71% vs. 88% and 82% vs. 93%). The specificity of both assays for both allergens was between 94% and 98%. Twenty‐nine patients that tested negative for rApi m 1 or rVes v 5 with CAP were positive with LITE, but none of the patients that tested negative with LITE were positive with CAP. The positive values of rApi m 1 and rVes v 5 were on average 2.7 and 2.3 times higher, with the LITE than with the CAP system. The combination of rApi m 1 and rApi m 2 (LITE) and the combination of rVes v 5 (LITE) and rVes v 1 (CAP) almost matched the sensitivity of native venoms (95% and 97%, respectively), whereas the diagnostic sensitivity of the combination of rVes v 5 and rVes v 1 (CAP) did not reach the sensitivity of rVes v 5 (LITE) alone (90% vs. 93%). IgE levels to venom recombinants and total IgE did not correlate with the severity of sting reaction.
Conclusions & Clinical Relevance
The use of rApi m 1 and rVes v 5 with the LITE system significantly enhanced diagnostic utility of venom recombinants and should improve the dissection of bee and yellow jacket venom allergy.
Background
The precise immunological mechanisms for the early clinical protection of venom immunotherapy (VIT) have not yet been explained. Our aim was to evaluate whether high‐affinity IgE receptor ...(FcεRI) and the related basophil function have a role in the induction of short‐term VIT protection.
Methods
We included 60 adults and 48 children. Basophil threshold sensitivity (CD‐sens) to anti‐FcεRI stimulation, and FcεRI gene and cell‐surface expression were assessed at the beginning and just before the first maintenance dose (MD) of 100 μg of ultra‐rush VIT (day 5) and at the beginning, during buildup, and just before the first MD of 70 μg and of 100 μg of semi‐rush VIT (weeks 1–2 and 5).
Results
We demonstrated a significant reduction in CD‐sens to anti‐FcεRI stimulation before the first MD in both ultra‐rush and semi‐rush VIT in all included subjects. FcεRI gene and/or cell‐surface expression was decreased in 34–100% of subjects, with different dynamics between VIT protocols.
Conclusion
We found a marked desensitization of FcεRI‐activated basophils after short‐term VIT. This suppression, which could be highly relevant for the development of early protective mechanisms, might be also related to the changes at the level of FcεRI expression.
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