Background
There is no in vitro test to predict the induction of long‐term tolerance in patients treated with venom immunotherapy (VIT). The aim of this study was to investigate whether ...immunotherapy‐induced changes in basophil responsiveness reflect a state of protection and the induction of a tolerance.
Methods
Twenty‐three patients with allergic reaction after Hymenoptera sting (11 wasp and 12 honeybee) were treated with VIT. In all patients, a CD63 basophil activation test was performed before the beginning of immunotherapy, after 1 year and after completing 4–6.5 years of immunotherapy (approximately 1 year after stopping). The tolerance was then evaluated by a sting challenge test. The basophil activation test was repeated 3–6 months after the challenge.
Results
Twenty‐two subjects showed a negative sting challenge, and one subject, a positive sting challenge. Allergen‐specific basophil response remained unchanged after 1 year of immunotherapy. However, after immunotherapy, a significant and approximately fourfold decrease was demonstrated in all tolerant subjects mainly in response to submaximal 0.1 μg/ml allergen concentration. This depression was sustained and did not change with the sting challenge test. In a nontolerant patient with a positive sting challenge, basophil response did not change.
Conclusions
Our results suggest that the depression of allergen‐specific basophil response seems to be associated with the induction of a tolerance after completing a course of VIT.
Tridacna derasa shells show a crossed lamellar microstructure consisting of three hierarchical lamellar structural orders. The mineral part is intimately intergrown with 0.9 wt% organics, namely ...polysaccharides, glycosylated and unglycosylated proteins and lipids, identified by Fourier transform infrared spectrometry. Transmission electron microscopy shows nanometre-sized grains with irregular grain boundaries and abundant voids. Twinning is observed across all spatial scales and results in a spread of the crystal orientation angles. Electron backscatter diffraction analysis shows a strong fibre texture with the 001 axes of aragonite aligned radially to the shell surface. The aragonitic 100 and 010 axes are oriented randomly around 001. The random orientation of anisotropic crystallographic directions in this plane reduces anisotropy of the Young's modulus and adds to the optimization of mechanical properties of bivalve shells.
Summary
Background
The effects of pollen immunotherapy on effector cells of allergic inflammation, such as mast cells and basophils, are poorly understood.
Objective
For this reason, we conducted an ...open study on basophil allergen threshold sensitivity during birch pollen immunotherapy.
Methods
Basophil sensitivity was measured by CD63 flow cytometry in 14 patients with moderate–severe intermittent birch pollen rhinitis using four log allergen concentrations. In nine patients, we analysed the basophil sensitivity before and during treatment with subcutaneous birch immunotherapy (perennial scheme with allergoid). We also included eight birch‐allergic donor subjects for IgG inhibition experiments and eight control subjects.
Results
There was a decrease in basophil allergen threshold sensitivity after 2, 3, and 5 months of immunotherapy. This decrease was correlated with an improvement in patients' symptoms measured on a visual analogue scale. The serum obtained after immunotherapy induced a significant decrease in allergen threshold sensitivity in donor birch‐allergic basophils. This inhibition was not observed after IgG depletion from the serum.
Conclusions
In this study, we showed that birch immunotherapy‐induced IgG antibodies are associated with a reduction in basophil allergen threshold sensitivity. Further studies are needed to show whether the changes in basophil sensitivity are of clinical relevance in pollen immunotherapy.
Cite this as: N. Lalek, M. Kosnik, M. Silar and P. Korosec, Clinical & Experimental Allergy, 2010 (40) 1186–1193.
An anaphylactic reaction due to a Hymenoptera sting is a clinical emergency, and patients, their caregivers as well as all healthcare professionals should be familiar with its recognition and acute ...management. This consensus report has been prepared by a European expert panel of the EAACI Interest Group of Insect Venom Hypersensitivity. It is targeted at allergists, clinical immunologists, internal medicine specialists, pediatricians, general practitioners, emergency department doctors, and any other healthcare professional involved. The aim was to report the scientific evidence on self‐medication of anaphylactic reactions due to Hymenoptera stings, to inform healthcare staff about appropriate patient self‐management of sting reactions, to propose indications for the prescription of an adrenaline auto‐injector (AAI), and to discuss other forms of medication. First‐line treatment for Hymenoptera sting anaphylaxis is intramuscular adrenaline. Prescription of AAIs is mandatory in the case of venom‐allergic patients who suffer from mast cell diseases or with an elevated baseline serum tryptase level and in untreated patients with a history of a systemic reaction involving at least two different organ systems. AAI prescription should also be considered in other specific situations before, during, and after stopping venom immunotherapy.
Summary
Background
Current guidelines do not adequately address the question of how best to manage patients with a convincing history of insect allergy, but negative venom‐specific IgE and skin test ...results.
Methods
Forty‐seven patients out of a total of 1219 (4%), with a positive history of sting allergy, were recruited over a period of 4.5 years. All recruited patients had a convincing history of a severe or a life‐threatening anaphylactic reaction of Mueller grade II–IV (median grade III) after Hymenoptera sting, but negative venom‐specific IgE and skin prick test results. Diagnostic work‐up was prospectively followed by the CD63 basophil activation test and by intradermal skin testing. A control group of 25 subjects was also assessed.
Results
Thirty‐five out of 47 (75%) patients demonstrated a positive basophil CD63 response after stimulation with bee and/or wasp venom. Intradermal venom skin tests were performed for 37 patients, 17 (46%) of whom showed positive results. Out of 20 patients who demonstrated negative intradermal test results, 12 patients showed a positive CD63 response (60%). In contrast, out of 9 patients who showed a negative CD63 response, only one was detected by intradermal testing (11%). In the control group, only two out of 25 (4%) subjects displayed a positive basophil response and/or intradermal test.
Conclusion
Here we show that, in complex cases with inconclusive diagnostic results, the CD63 activation test could be particularly useful and more sensitive than intradermal skin testing.
Global diversity curves reflect more than just the number of taxa that have existed through time: they also mirror variation in the nature of the fossil record and the way the record is reported. ...These sampling effects are best quantified by assembling and analyzing large numbers of locality-specific biotic inventories. Here, we introduce a new database of this kind for the Phanerozoic fossil record of marine invertebrates. We apply four substantially distinct analytical methods that estimate taxonomic diversity by quantifying and correcting for variation through time in the number and nature of inventories. Variation introduced by the use of two dramatically different counting protocols also is explored. We present sampling-standardized diversity estimates for two long intervals that sum to 300 Myr (Middle Ordovician-Carboniferous; Late Jurassic-Paleogene). Our new curves differ considerably from traditional, synoptic curves. For example, some of them imply unexpectedly low late Cretaceous and early Tertiary diversity levels. However, such factors as the current emphasis in the database on North America and Europe still obscure our view of the global history of marine biodiversity. These limitations will be addressed as the database and methods are refined.
Summary
Background
The mechanisms responsible for the difference between clinically irrelevant IgE‐sensitization and allergic rhinitis are not fully understood.
Objective
We evaluated the humoral and ...cellular mechanisms that may be associated with the presence of allergic rhinitis symptoms.
Methods
We selected 26 subjects with positive grass pollen skin tests and IgE antibodies to Timothy (g6) and the major grass allergens rPhl p 1, 5b. Fourteen of those patients reported a history of allergic rhinitis. During winter, we performed a grass pollen CD63 basophile activation test using four log allergen concentrations, followed by a grass nasal provocation test (NPT). We obtained symptom scores in the subsequent pollination season.
Results
We showed that subjects with a positive NPT have significantly higher CD63 basophile grass pollen responsiveness than NPT‐negative subjects, preferably at submaximal allergen concentrations, which represent cellular sensitivity. Moreover, basophile sensitivity positively correlated with the size of the grass‐specific IgE fraction in relation to total IgE, and it was highly predictive of allergic rhinitis symptoms in the following pollination season.
Conclusion and Clinical Relevance
Allergic rhinitis symptoms are significantly associated with allergen‐specific basophile sensitivity. In vitro evaluation of basophile sensitivity should prove useful for distinguishing clinical phenotype of allergic sensitization.
Background
An important advantage of allergen immunotherapy as compared to pharmacotherapy for allergic rhinitis is the long‐term effect that persists after completing immunotherapy. The mechanism of ...the sustained effect of allergen immunotherapy is not completely understood.
Methods
We conducted a 7‐year study of monitoring allergen‐specific basophil response and serological markers in 20 subjects with moderate‐to‐severe grass pollen‐allergic rhinitis just before beginning and after up‐dosing of subcutaneous grass pollen immunotherapy, before the first pollen season, and 1–2 years after completion of 3–5 years of treatment. Comparable untreated rhinitis subjects were followed at the same time points. Clinical outcomes included assessment of symptoms, use of rescue medication, and quality of life. The basophil response was also monitored after removal of IgG antibodies.
Results
Basophil response assessed as area under the curve (AUC) halved during initiation of SCIT and was 55% lower 1–2 years after completing SCIT. In the untreated group, the basophil response remained comparable. Although immunotherapy‐induced grass pollen‐specific IgG4 levels decreased to near pre‐immunotherapy levels after completing SCIT, the removal of IgG antibodies resulted in an increase in basophil response almost to the pre‐immunotherapy levels. In untreated subjects, removal of IgG did not have any effect on basophil response.
Conclusions
Grass pollen immunotherapy induces sustained suppression of the allergen‐specific basophil response that persists after completion of treatment and could account for long‐term clinical tolerance. It also seems to be associated with persistent blocking activity of IgG antibodies.
Angiogenesis is a prominent feature of structural tissue remodelling that occurs in chronic airway diseases, including chronic obstructive pulmonary disease (COPD). The aim of this study was to ...evaluate the airway levels of VEGF, angiogenin, IL‐8 and TNF‐α in patients with COPD during the stable phase and during acute exacerbation of the disease. We analysed induced sputum samples from 28 patients with COPD. Thirteen of these patients were followed up and second samples of sputum were obtained during acute exacerbation of the disease. The two control groups consisted of 12 healthy smokers and seven healthy non‐smokers, all with normal lung function tests. Concentrations of VEGF, angiogenin, IL‐8, TNF‐α and bFGF were measured by cytometric bead array. In the induced sputum of patients with stable COPD, concentrations of VEGF (P < 0.001, P = 0.02), angiogenin (P < 0.0001, P < 0.0001), IL‐8 (P < 0.0001, P = 0.0021) and TNF‐α (P < 0.001, P = 0.03) were significantly elevated in comparison with healthy smokers and non‐smokers. No additional elevation of angiogenic factors was demonstrated at the time of exacerbation. There was a significant negative correlation between FEV1 and VEGF (P < 0.05, r = −0.38), angiogenin (P < 0.0001, r = −0.68) and IL‐8 (P < 0.001, r = −0.54) among smokers (smoking COPD patients and healthy smokers). No significant differences were observed between groups of healthy smokers and non‐smokers. These results showed increased airway angiogenesis in patients with COPD. Moreover, VEGF, IL‐8 and angiogenin negatively correlated with pulmonary function, which suggests their important role in COPD airway remodelling. However, no additional angiogenic activation was found during exacerbation of COPD.
Background: Systemic side‐effects of venom immunotherapy (VIT) represent a considerable problem in the treatment of patients allergic to Hymenoptera venom. We examined the hypothesis whether ...basophil responsiveness might be connected with the adverse reactions to VIT.
Methods: Basophil surface expression of activation marker CD63 induced by different concentrations of honeybee and wasp venom (0.1 and 1 μg/ml) was measured by flow cytometry in 34 patients with history of systemic anaphylactic reactions to Hymenoptera sting just before rush honeybee or wasp VIT.
Results: Eleven of 34 patients had systemic anaphylactic reaction (Mueller grades I–III) and one patient a large local reaction to VIT. In those 12 patients, median percentage of activated basophils after stimulation with VIT‐specific venom in concentration of 0.1 μg/ml was 99% (range: 17–195) of value reached with stimulation with 1 μg/ml. Side‐effects occurred in all patients with 0.1/1 ratios over 92% (eight of 12). In contrast, in 22 patients with no side‐effects, the median 0.1/1 ratio was 25% (range: 2–92). These concentration‐dependent activation ratios were significantly different between the groups with and without side reactions (P < 0.0001). We also show significant positive correlation of the occurrence/clinical grade of the side‐effects with individual ratios of CD63 basophil response (r = 0.73, P < 0.0001).
Conclusion: The results suggest that increased basophil sensitivity to allergen‐specific in vitro stimulation is significantly associated with major side‐effects of VIT.
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