Clinical profile of idiopathic angioedema based on severity and treatment response is independent of the presence of concomitant wheals

Background: Idiopathic angioedema varies in disease severity and treatment response, possibly due to different pathophysiological mechanisms. The presence of wheals is an indicator for histamine-mediated angioedema. Idiopathic angioedema patients are treated in accordance with chronic spontaneous urticaria guidelines. Little is known about treatment effectiveness in idiopathic angioedema patients without wheals in comparison to idiopathic angioedema patients with concomitant wheals. Objective: To describe the disease severity profile in patients with angioedema of unknown cause in relation to prophylactic treatment and the presence or absence of concomitant wheals. Methods: In this retrospective cohort study, all records of angioedema patients visiting the outpatient clinic of the UMC Utrecht between January 2015 and March 2020 were screened. Patients with idiopathic angioedema, including those with concomitant wheals, were included. Attack frequency, patient-reported disease control and attack treatment as indicator for severity were analysed in relation to prophylactic treatment at follow-up and outcomes were compared between patients with and without concomitant subordinary wheals. Results: Two hundred thirty-six patients were included: 95% (139/236) with angioedema only and 41% (97/236) with angioedema and concomitant subordinary wheals. No prophylactic treatment was prescribed in 27% (64/236), with well-controlled disease in 86% (25/29) of patients. Antihistamine monotherapy was used in 59% (139/236) of patients and resulted in well-controlled disease in 68% (62/92). Add-on treatment was prescribed in 14% (33/236) of patients, omalizumab in 9% (22/236) specifically, with complete response in 38% (6/16) of patients and low attack frequency in another 18% (3/16). Difficult-to-treat disease was seen in 8% (18/236), with no response to a fourfold dose of antihistamines or omalizumab. All findings were independent from the presence of concomitant wheals. Conclusion: Angioedema is well manageable in the majority of patients without prophylactic therapy or antihistamine monotherapy, but a substantial proportion does not respond to antihistamines and/or omalizumab. Treatment response was independent of the presence or absence of concomitant wheals

Assessment of allelic diversity in intron-containing Mal d 1 genes and their association to apple allergenicity

<p>Abstract</p> <p>Background</p> <p>Mal d 1 is a major apple allergen causing food allergic symptoms of the oral allergy syndrome (OAS) in birch-pollen sensitised patients. The <it>Mal d 1 </it>gene family is known to have at least 7 intron-containing and 11 intronless members that have been mapped in clusters on three linkage groups. In this study, the allelic diversity of the seven intron-containing <it>Mal d 1 </it>genes was assessed among a set of apple cultivars by sequencing or indirectly through pedigree genotyping. Protein variant constitutions were subsequently compared with <b>S</b>kin <b>P</b>rick <b>T</b>est (SPT) responses to study the association of deduced protein variants with allergenicity in a set of 14 cultivars.</p> <p>Results</p> <p>From the seven intron-containing <it>Mal d 1 </it>genes investigated, <it>Mal d 1.01 </it>and <it>Mal d 1.02 </it>were highly conserved, as nine out of ten cultivars coded for the same protein variant, while only one cultivar coded for a second variant. <it>Mal d 1.04</it>, <it>Mal d 1.05 </it>and <it>Mal d 1.06 A, B </it>and <it>C </it>were more variable, coding for three to six different protein variants. Comparison of <it>Mal d 1 </it>allelic composition between the high-allergenic cultivar Golden Delicious and the low-allergenic cultivars Santana and Priscilla, which are linked in pedigree, showed an association between the protein variants coded by the <it>Mal d 1.04 </it>and <it>-1.06A </it>genes (both located on linkage group 16) with allergenicity. This association was confirmed in 10 other cultivars. In addition, <it>Mal d 1.06A </it>allele dosage effects associated with the degree of allergenicity based on prick to prick testing. Conversely, no associations were observed for the protein variants coded by the <it>Mal d 1.01 </it>(on linkage group 13), -<it>1.02</it>, -<it>1.06B, -1.06C </it>genes (all on linkage group 16), nor by the <it>Mal d 1.05 </it>gene (on linkage group 6).</p> <p>Conclusion</p> <p>Protein variant compositions of Mal d 1.04 and -1.06A and, in case of <it>Mal d 1.06A</it>, allele doses are associated with the differences in allergenicity among fourteen apple cultivars. This information indicates the involvement of qualitative as well as quantitative factors in allergenicity and warrants further research in the relative importance of quantitative and qualitative aspects of <it>Mal d 1 </it>gene expression on allergenicity. Results from this study have implications for medical diagnostics, immunotherapy, clinical research and breeding schemes for new hypo-allergenic cultivars.</p

Thresholds of allergenic proteins in foods

Threshold doses or Estimated Eliciting Doses (EEDs) represent an important new field of research in food allergy. Clinicians and regulators have embraced some toxicological concepts such as LOAEL and NOAEL and applied them to an area of significant clinical uncertainty and interest. The impact of intrinsic human factors (e.g., asthma and exercise) and extrinsic event factors (e.g., season, location and especially dose of allergen) on a future allergic reaction in the community needs to be considered carefully when interpreting results of clinical and research low-dose food challenges. The ongoing cooperation of food allergy research groups in medicine, food science and government will surely deliver results of the highest importance to the wider communities of allergology, food science and technology and the increasing number of allergic consumers

Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1

Background: Individual amino acid residues of the major birch pollen allergen, Bet v 1, have been identified to be crucial for IgE recognition. The objective of the present study was to evaluate whether this concept was applicable for the Bet v 1-homologous apple allergen, Mal d 1. Methods: A Mal d 1 five-point mutant was produced by PCR techniques, cloned into pMW 172 and expressed in Escherichia coli BL21(DE3) cells. To evaluate the allergenic properties of the engineered protein compared to Mal d 1 wild-type IgE immunoblotting, ELISA, peripheral blood monocytes proliferation assays, and skin prick tests were performed. Results: The Mal d 1 mutant showed reduced capacity to bind specific IgE as compared to wild-type Mal d 1 in in vitro assays in the majority of the sera tested. In ELISA, 10 out of 14 serum samples displayed an 88-30% decrease in IgE binding to Mal d 1 mutant compared to wild-type Mal d 1. Skin prick tests in apple-allergic patients (n = 2) confirmed the markedly decreased ability of the Mal d 1 mutant to induce allergic reactions in vivo. However, the relevant T cell epitopes were present in the mutated molecule according to peripheral blood mononuclear cell proliferation assays. Conclusions: Our findings suggest that it is possible to modulate the IgE-binding properties of allergens by single amino acid substitutions at crucial positions which might be useful for future immunotherapy of birch-pollen-associated food allergies which are not ameliorated by birch pollen immunotherapy. Copyright (C) 2006 S. Karger AG, Basel

Food allergen sensitization pattern in adults in relation to severity of atopic dermatitis

BACKGROUND: Limited data are available on the frequency of IgE mediated food sensitization and food allergy (FA) in adults with atopic dermatitis (AD). OBJECTIVE: We investigated the pattern of food sensitization in adults with AD in relation to AD severity using multiplexed allergen microarray. METHODS: 211 adult patients referred between January 2010-July 2011 for evaluation of AD were unselectively included. Severity of AD was determined by therapy intensity, SASSAD-skin-score and sTARC levels. Allergen specific sIgE levels were measured by ImmunoCAP ISAC® microarray. FA was defined as convincing history taken by physician and sensitization to the corresponding allergen. RESULTS: Sensitization to food was found in 74.4% of the AD patients, 54% had a positive history of FA and 20.4% asymptomatic sensitization. There was no association between severity of AD and frequency of food sensitization or history of FA. Sensitization to PR-10 related food allergens occurred most frequently (63.5%) and was independent from AD severity. Correspondingly, pollen-food syndrome accounted for most of the FA, being also independent from AD severity. Of all plant food allergens only sensitization to nAra h 1 was significantly more frequent in patients with severe AD. In the total group 75 (35.5%) patients with AD showed sensitization to any animal food allergen. The percentage was significantly higher in patients with severe AD (51.4%) compared to patients with mild/moderate AD (27.7%). Sensitization to cow’s milk allergens, in particular to nBos d lactoferrin, was more frequent in severe AD patients. CONCLUSION: AD was frequently associated with food sensitization. The percentage of sensitization to animal food allergens was significantly higher in severe AD patients