The major allergens of birch pollen and cow milk, Bet v 1 and Bos d 5, are structurally related to human licocalin 2, enabling them to manipulate T-helper cells depending on their load with siderophore-bound iron

We conclude that Bet v 1 and Bos d 5 not only structurally mimic human LCN2, but also functionally by their ability to bind iron via siderophores. The apo-forms promote Th2 cells, whereas the holo-forms appear to be immunosuppressive. These results provide for the first time a functional understanding on the principle of allergenicity of major allergens from entirely independent sources, like birch and milk

World Allergy Organization Journal / Clinical efficacy of sublingual immunotherapy is associated with restoration of steady-state serum lipocalin 2 after SLIT : a pilot study

Background: So far, only a few biomarkers in allergen immunotherapy exist that are associated with a clinical benefit. We thus investigated in a pilot study whether innate molecules such as the molecule lipocalin-2 (LCN2), with implications in immune tolerance demonstrated in other fields, may discriminate A) between allergic and non-allergic individuals, and B) between patients clinically responding or non-responding to sublingual allergen immunotherapy (SLIT) with house dust mite (HDM) extract. Moreover, we assessed haematological changes potentially correlating with allergic symptoms. Methods: LCN2-concentrations were assessed in sera of healthy and allergic subjects (n = 126) as well as of house dust mite (HDM) allergics before and during HDM- sublingual immunotherapy (SLIT) in a randomized, double-blind, placebo-controlled trial for 24 weeks. Sera pre-SLIT (week 0), post-SLIT (week 24) and 9 months after SLIT were assessed for LCN2 levels and correlated with total nasal symptom scores (TNSS) obtained during chamber challenge at week 24 in patients receiving HDM- (n = 31) or placebo-SLIT (n = 10). Results: Allergic individuals had significantly (p < 0.0001) lower LCN2-levels than healthy controls. HDM-allergic patients who received HDM-SLIT showed a significant increase in LCN2 9 months after termination of HDM-SLIT (p < 0.001), whereas in subjects receiving placebo no increase in LCN2 was observed. Among blood parameters a lower absolute rise in the lymphocyte population (p < 0.05) negatively correlated with symptom improvement (Pearson r 0.3395), and a lower relative increase in the neutrophils were associated with improvement in TNSS (p < 0.05). LCN2 levels 9 months after immunotherapy showed a low positive correlation with the relative improvement of symptoms (Pearson r 0.3293). LCN2-levels 9 months off-SLIT were significantly higher in patients whose symptoms improved during chamber challenge than in those whose symptoms aggravated (p < 0.01). Conclusion: Serum LCN2 concentrations 9 months off-SLIT correlated with clinical reactivity in allergic patients. An increase in the LCN2 levels 9 months after HDM-SLIT was associated with a clinical benefit. Serum LCN2 may thus contribute to assess clinical reactivity in allergic patients. Trial registration: Part of the data were generated from clinicaltrials.gov Identifier NCT01644617.(VLID)468365

Edible insects: Cross-recognition of IgE from crustacean- and house dust mite allergic patients, and reduction of allergenicity by food processing

Background: Insects have become increasingly interesting as alternative nutrient sources for feeding humans and animals, most reasonably in processed form. Initially, some safety aspects — among them allergenicity — need to be addressed. Objective: To reveal the cross-reactivity of shrimp-, mite- and flies-allergic patients to different edible insects, and further to assess the efficacy of food processing in reducing the recognition of insect proteins by patients' IgE and in skin prick testing of shrimp-allergic patients. Methods: IgE from patients allergic to crustaceans, house dust mite or flies was evaluated for cross-recognition of proteins in house cricket Acheta domesticus (AD), desert locust Schistocerca gregaria (SG) and Yellow mealworm Tenebrio molitor (TM). Changes in IgE-binding and SPT-reactivity to processed insect extracts were determined for migratory locust (Locusta migratoria, LM), after different extraction methods, enzymatic hydrolysis, and thermal processing were applied. Results: IgE from patients with crustacean-allergy shows cross-recognition of AD, SG and stable flies; house dust mite allergics' IgE binds to AD and SG; and the flies-allergic patient recognized cricket, desert locust and migratory locust. Cross-reactivity and allergenicity in SPT to LM can be deleted by conventional processing steps, such as hydrolysis with different enzymes or heat treatment, during the preparation of protein concentrates. Conclusion: The results show that crustacean-, HDM- and stable flies-allergic patients cross-recognize desert locust and house cricket proteins, and crustacean-allergic patients also flies proteins. Furthermore, this study shows that appropriate food processing methods can reduce the risk of cross-reactivity and allergenicity of edible insects. Keywords: Allergenicity, Cross-recognition, Edible insects, Enzymatic hydrolysis, Food allergy, Immunoreactivity, Thermal processin

Elevated oxytocin and noradrenaline indicate higher stress levels in allergic rhinitis patients: Implications for the skin prick diagnosis in a pilot study

Background & Aims The effects of acute stress on allergic symptoms are little understood. The intention of this clinical study was to study the effects of acute stress and related mediators in allergic rhinitis (AR), taking the wheal and flare reaction in skin prick testing (SPT) as a readout. Methods 19 healthy and 21 AR patients were first subjected to SPTs with grass pollen-, birch pollen- and house dust mite allergen extracts, histamine and negative control. Subsequently, participants were exposed to a standardized Trier Social Stress Test (TSST), followed by SPT on the contralateral forearm. Stress responders were identified based on the salivary cortisol levels and State-subscale of State-Trait-Anxiety Inventory (STAI-S). Blood samples were collected before and after TSST and adrenaline, noradrenaline, serotonin, oxytocin, platelet activating factor and prostaglandin D2 were analyzed by enzyme immunoassay (EIA). Results SPT results of 14/21 allergics and 11/19 healthy who responded with stress after TSST were evaluated. No significant differences regarding SPT to allergens or histamine before and after the stress test could be calculated at the group level. But, the wheal and flare sizes after TSST increased or decreased substantially in several individuals, and unmasked sensitization in one healthy person, which could not be correlated with any mediator tested. The most significant finding, however, was that, independent of TSST, the baseline levels of oxytocin and noradrenaline were significantly higher in allergics. Conclusion High baseline levels of noradrenaline points toward higher stress levels in allergic patients, which might be counterregulated by elevated oxytocin. Moreover, our data indicate that acute stress may have a significant influence on SPT fidelity in susceptible individuals

Verification of TSST-induced stress in study subjects.

<p><b>a)</b> Salivary cortisol (means ± SD, ng/ml) in allergics (n = 14) and non-allergics (n = 11) who responded after the TSST; grey data points before, black after TSST; <b>b)</b> results of State-Trait-Anxiety Inventory (STAI-S) for self-reported anxiety in allergic (n = 20) and non-allergic participants (n = 19) before (grey boxes) and after the TSST (black boxes) (means ± SD); ***p ≤ 0.001. *P ≤ 0.05.</p

Characterization and clinical description of study participants.

<p>Characterization and clinical description of study participants.</p

Comparison of SPT results in the allergic and healthy cohort before and after the TSST.

<p>Comparison of SPT results in the allergic and healthy cohort before and after the TSST.</p

Changes in SPT wheal diameters before and after the TSST.

<p><b>a)</b> Box plots illustrating changes in wheal diameters before (grey boxes) and after TSST (black) in the allergic cohort, in mm (y-axis); <b>b)</b> Individual changes in SPT wheal diameters to birch pollen (BP) (n = 8), <b>c)</b> grass pollen (GP) (n = 8), <b>d)</b> house dust mite (HDM) (n = 10), before (Pre) and after the TSST (Post); black lines in <b>b)-d)</b> indicate subjects responding with >10% relative change of reactivity, grey: less than 10% change.</p