A preliminary study suggests that intestinal-wall assessment by means of noninvasive multispectral optoacoustic tomography may distinguish remission from active disease in patients with Crohn’s ...disease.
To the Editor:
In chronic inflammatory diseases, uncontrolled inflammation is associated with increased rates of hospitalization, complications, and death. Because of the potential severity of these conditions, there is an increased demand for new diagnostic approaches.
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Multispectral optoacoustic tomography (MSOT) is a new imaging technique that permits the noninvasive quantification of hemoglobin-dependent tissue perfusion and oxygenation as surrogates of inflammation.
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This approach uses the excitation of short-pulsed laser light with near-infrared wavelengths to induce the photoacoustic effect in targeted tissues, which results in detectable sound waves induced by thermoelastic expansion.
In this single-center, cross-sectional diagnostic study (ClinicalTrials.gov number, NCT02622139), . . .
Background Patients with birch pollen allergy often develop allergic reactions to plant foods. Objective To evaluate the prevalence, main symptoms, and triggers of birch pollen–related food allergy ...and the role of food-specific IgG4 antibodies in food tolerance. Methods Food-induced symptoms were evaluated in 225 individuals with birch pollen allergy by using a standardized questionnaire. IgE and IgG4 levels specific for the major birch pollen allergen Bet v 1 and birch profilin Bet v 2 and the Bet v 1 homologs in apple (Mal d 1) and hazelnut (Cor a 1) were quantified by ImmunoCAP. Mock-treated and IgG-depleted sera from patients tolerating hazelnuts in food challenges were compared for their inhibitory activity for binding of Cor a 1–IgE complexes to B cells. Results In total, 73% of the study population experienced food allergy, which was perennial in 86% of the affected individuals. The oral allergy syndrome was the main clinical manifestation. However, more than 58% of the patients also experienced food-induced rhinoconjunctivitis. Apples and hazelnuts were identified as the most frequent triggers. Food allergy correlated with IgE reactivity to Bet v 1 but not to Bet v 2. Mal d 1–specific and Cor a 1–specific IgG4 /IgE ratios were significantly higher in food-tolerant individuals than individuals with food allergy. Sera from IgG4 -positive food-tolerant patients possessed IgG-dependent IgE-inhibitory activity. Conclusion Birch pollen–related food allergy is highly prevalent and often perennial. High food allergen–specific IgG4 /IgE ratios seem associated with food tolerance, potentially because specific IgG4 blocks IgE binding to food allergens. Thus, the presence of food allergen–specific IgG4 antibodies is no diagnostic marker for birch pollen–related food allergy.
Background Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. Objective Our aim was to evaluate the association of baseline serum ...tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. Methods In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. Results Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. Conclusion In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.
Background Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors. Objective Our aim was to evaluate the association of baseline serum tryptase ...concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT. Methods In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models. Results Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy. Conclusion Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.
Allergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment ...of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear.
Here we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure.
Subjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG1-4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter.
Nasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects.
In conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure.
http://clinicaltrials.gov/NCT00755066.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To the Editor: Allergen-specific IgE antibodies are key elements in allergic inflammation and in the immunoregulation of allergic disease.1 Mucosal allergen contact induces allergic inflammation and ...also boosts systemic allergen-specific IgE production, which leads to increased sensitivity of mast cells and basophils, to the upregulation of Fcε receptor expression on allergic effector cells and antigen-presenting cells, and thus to increased T-cell activation.1-3 Increases in allergen-specific IgE levels are also associated with increased clinical sensitivity and aggravation of symptoms.4,5 Unwanted boosts of allergen-specific IgE production occur during seasonal allergen contact through the respiratory mucosa, which can be reproduced in clinical studies by controlled nasal allergen provocation.4 However, strong boosts of IgE production are also observed in the course of allergen-specific immunotherapy, reaching up to 5-fold of pretreatment levels, for example, after sublingual immunotherapy when allergens are applied through the mucosa.6 In immunotherapy studies performed with recombinant allergen derivatives, which have been engineered to eliminate IgE reactivity and to preserve specific T-cell epitopes, only mild boosts of allergen-specific IgE production were observed that did not cause clinically relevant sensitization.7,8 Here we conducted a nasal provocation test study with rBet v 1, the major allergen of birch pollen, and 2 non-IgE-reactive rBet v 1 fragments.
Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These ...derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.
Background Patients with birch pollen allergy often develop allergic reactions to plant foods. Objective To evaluate the prevalence, main symptoms, and triggers of birch pollen-related food allergy ...and the role of food-specific IgG4antibodies in food tolerance. Methods Food-induced symptoms were evaluated in 225 individuals with birch pollen allergy by using a standardized questionnaire. IgE and IgG4levels specific for the major birch pollen allergen Bet v 1 and birch profilin Bet v 2 and the Bet v 1 homologs in apple (Mal d 1) and hazelnut (Cor a 1) were quantified by ImmunoCAP. Mock-treated and IgG-depleted sera from patients tolerating hazelnuts in food challenges were compared for their inhibitory activity for binding of Cor a 1-IgE complexes to B cells. Results In total, 73% of the study population experienced food allergy, which was perennial in 86% of the affected individuals. The oral allergy syndrome was the main clinical manifestation. However, more than 58% of the patients also experienced food-induced rhinoconjunctivitis. Apples and hazelnuts were identified as the most frequent triggers. Food allergy correlated with IgE reactivity to Bet v 1 but not to Bet v 2. Mal d 1-specific and Cor a 1-specific IgG4/IgE ratios were significantly higher in food-tolerant individuals than individuals with food allergy. Sera from IgG4-positive food-tolerant patients possessed IgG-dependent IgE-inhibitory activity. Conclusion Birch pollen-related food allergy is highly prevalent and often perennial. High food allergen-specific IgG4/IgE ratios seem associated with food tolerance, potentially because specific IgG4blocks IgE binding to food allergens. Thus, the presence of food allergen-specific IgG4antibodies is no diagnostic marker for birch pollen-related food allergy.