Morten Christensen

Patterns of suspected wheat-related allergy: a retrospective single-centre case note review in 156 patients

BackgroundAllergy to wheat can present clinically in different forms: Sensitization to ingested wheat via the gastrointestinal tract can cause traditional food allergy or in combination with exercise, Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA). Sensitization to inhaled wheat flour may lead to occupational rhinitis and/or asthma.MethodsWe retrospectively reviewed the case notes of 156 patients (age 0.7 – 73.3xa0years) with a case history of wheat allergy. The population was divided into three groups, 1: Wheat allergy elicited by ingestion, 2: By inhalation and 3: WDEIA. All patients were examined with detailed case history, specific IgE (sIgE), Skin Prick Test (SPT) and wheat challenge (nasal or oralu2009±u2009exercise). Details of the case history were extracted from the patients´ case records.ResultsGroup 1: Twenty one of 95 patients were challenge positive (15 children, 6 adults). All children had atopic dermatitis, and most (13/15) outgrew their wheat allergy. Most children (13/15) had other food allergies. Challenge positive patients showed significantly higher levels of sIgE to wheat and significantly more were SPT positive than challenge negative.Group 2: Eleven out of 13 adults with occupational asthma or rhinitis were challenge positive. None outgrew their allergy. Seven had positive sIgE and 10 had positive SPT to wheat.Group 3: Ten of 48 (adolescent/adults) were positive when challenged during exercise. Challenge positive patients showed significantly higher levels of sIgE to ω-5-gliadin. The natural course is presently unknown.ConclusionWheat allergy can manifest in different disease entities, rendering a detailed case history and challenge mandatory. Patient age, occupation, concomitant allergies (food or inhalant) and atopic dermatitis are important factors for evaluation.

Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols

We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (±0.17)×10-6cm/s. When 0.1mM β-sitosterol was solubilized alongside, Papp was effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp=0.06 (±0.06)×10-6cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Papp in the range of 0-0.09×10-6cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.

Exercise Lowers Threshold and Increases Severity, but Wheat-Dependent, Exercise-Induced Anaphylaxis Can Be Elicited at Rest

BACKGROUNDnWheat-dependent, exercise-induced anaphylaxis (WDEIA) is a severe form of allergy in which exercise is being considered as mandatory. The diagnosis is often complex and the clinical reproducibility low.nnnOBJECTIVEnThe aims of this study were to establish a standardized challenge method for the diagnosis of WDEIA and to investigate whether exercise is an essential trigger factor or alternatively an augmentation factor able to lower threshold and increase severity.nnnMETHODSnWe investigated 71 patients (age, 18.6-73.7 years) with a case history of WDEIA. Skin prick test (SPT) and measurement of specific IgE (sIgE) were followed by an oral food challenge with gluten at rest and in combination with treadmill exercise.nnnRESULTSnA clinical reaction was elicited in 47 of 71 (66%), and in 26 of these (37%) the reaction could be elicited at rest. The median dose required at rest was 48 g (8-80 g) and in combination with exercise 24 g (4-80 g). Severity was significantly higher with exercise (2.3) than at rest (1.1) using Sampson severity score. In the challenge, SPT was positive to wheat in 93.6% (44 of 47) and to gluten in 95.7% (45 of 47). sIgE to wheat, gliadin, and omega-5 gliadin was present in 78.7% (37 of 47), 76.5% (36 of 47), and 91.4% (43 of 47) of the patients. Receiver operating characteristic-curve analysis for sIgE to omega-5 gliadin, a component of the gluten fraction and the major allergen in WDEIA, showed best sensitivity (91%) and specificity (92%) when gluten was combined with exercise.nnnCONCLUSIONSnA challenge test with gluten at rest and combined exercise is a safe confirmatory test for WDEIA. A reaction can be elicited at rest (without exercise), but exercise is able to lower the threshold and increase the severity.

Wheat-Dependent Cofactor-Augmented Anaphylaxis: A Prospective Study of Exercise, Aspirin, and Alcohol Efficacy as Cofactors

BACKGROUNDnWheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe and potentially life-threatening allergy caused by wheat ingestion and most commonly in combination with exercise.nnnOBJECTIVEnTo investigate the role and impact of different cofactors (exercise, aspirin, and alcohol) in patients with WDEIA.nnnMETHODSnWe studied 25 adult patients with WDEIA. Diagnostic workup included specific IgE to omega-5 gliadin and skin prick test with wheat flour and gluten. Titrated oral challenge was performed with gluten at rest, combined with treadmill exercise, aspirin, alcohol, or a combination of exercise and aspirin.nnnRESULTSnA positive challenge to gluten was found at rest (without cofactors) in 48% (12 of 25), with exercise in 92% (23 of 25), with aspirin in 84% (21 of 25), with alcohol in 56% (9 of 19), and with a combination of exercise and aspirin in 82% (18 of 22) of the patients. With exercise as a cofactor, the median threshold was 24 g (range, 4.8-80 g), with aspirin 8 g (range, 2.4-80 g), and with alcohol 28 g (range, 0-45 g). The combination of 2 cofactors (exercise and aspirin) resulted in a median threshold of 4.3 g (range, 1.1-48 g). The threshold for the clinical reaction was lowered by 63%, 83%, 36%, and 87%, respectively, compared with at rest. The mean severity grade (scale 0-5) according to the Sampson severity score at rest was 0.8 (range, 0-2), and when combined with exercise 2.1 (range, 0-5), with aspirin 1.9 (range, 0-5), with alcohol 0.8 (range, 0-2), and with the combination of exercise and aspirin 1.5 (range, 0-2).nnnCONCLUSIONnOur results demonstrate that exercise and aspirin augment clinical reactions in WDEIA by lowering the threshold and increase the severity of the allergic reaction, whereas alcohol gives ambiguous results. Furthermore, a combination of 2 cofactors (exercise and aspirin) increases thexa0risk of reactions.

Clinical relevance of sensitization to hydrolyzed wheat protein in wheat-sensitized subjects

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Data for the size of cholesterol-fat micelles as a function of bile salt concentration and the physico-chemical properties of six liquid experimental pine-derived phytosterol formulations in a cholesterol-containing artificial intestine fluid

The data in this paper are additional information to the research article entiltled “Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols” (Yi et al.,2016) [1]. The data derived from the measurement on six liquid formulations of commercial pine-derived phytosterol (CPP) by dynamic light scattering. The data cover micelle size and the zeta-potential for formulations with cholesterol including monoglyceride, oleic acid, and bile salt. The data demonstrate the critical effect of the bile salt concentration on the size of cholesterol-digested fat micelles.

A clinical reaction can be elicited without cofactors in Wheat dependent exercise induced anaphylaxis

Background: A body of evidence indicates that epigenetic modifications, including DNA methylation, play relevant roles in the differentiation and functions of immune cells. Therefore, these modifications have been increasingly implicated in the pathophysiology of allergic diseases. However, little is known about changes in DNA methylation during oral immunotherapy (OIT) in young children with food allergies. Here, we present genome-wide data of DNA methylation before and after OIT. Method: We gave rush OIT to two pediatric patients with egg allergy. Both the patients became tolerant and could consume eggs 1 year after the initiation of the therapy. CD14-positive monocytes and CD4-positive T cells were positively selected from peripheral blood mononuclear cells by magnetic bead-conjugated antibodies before and one year after starting OIT. Genomic DNA was purified from these cells and subjected to the Infinium Methylation Assay (Illumina). Results: A significant number of methylation-targeted CpG sites were found to be differentially methylated between the monocytes and T cells indicating that the cells represent different epigenetic profiles. DNA methylation profiles before and after starting OIT in the same type of cells were better correlated to each other than those between the two patients either before or after OIT. Gene ontology analysis of genes that displayed significant changes in methylation of promoter sequences in T cells showed that genes involved in the MAPK pathway were enriched the most. Conclusion: These results provide evidence that epigenetics plays a role in acquiring immune tolerance during OIT and can help further our understanding of the mechanisms involved in the immune tolerance of food allergy. 2 Grass pollen subcutaneous and sublingual immunotherapy inhibit allergen-induced nasal responses and local Th2 cytokines: a randomised controlled trialCharacterization of dose-FEV1 response of tralokinumab, an investigational anti-IL13 monoclonal antibody in patients with uncontrolled asthma : a population pharmacokinetic/pharmacodynamic modeling analysis