Scientific Reports / Sublingual house dust mite immunotherapy has no impact on decrease of circulating erythrocytes upon airway allergen challenge in allergic rhinitis

House dust mite (HDM) allergy is a predominant cause for perennial allergic rhinitis (AR) in Europe. We recently reported that circulating erythrocyte numbers decrease after airway allergen challenge in a murine asthma model and in grass-pollen sensitized AR subjects. Consequently, we aimed to evaluate these findings in HDM sensitized AR subjects and the influence of preceding allergen immunotherapy. Seventy-seven (age 26.87.3 years; 54.5% female) HDM-allergic rhinitis subjects previously enrolled in a randomized, monocentric sublingual immunotherapy (SLIT) trial at the Vienna Challenge Chamber (VCC) were included. Subjects had either received placebo (n=22), low-dose HDM (n=29) or high-dose HDM specific sublingual immunotherapy (n=26) daily for 24 weeks. Blood sampling was performed before and after 6hours of HDM allergen exposure. Overall, specific airway allergen challenge resulted in a significant decrease in circulating erythrocytes and hematocrit (p<0.001), and elevation of leukocytes (p<0.001), particularly segmented neutrophils (p<0.001). Gender had no significant effect on the observed changes in circulating blood cells. Erythrocytes decreased and neutrophil counts increased significantly after airway allergen challenge regardless of preceding immunotherapy. These findings imply a rapid systemic mobilization of neutrophils occurring within immediate type hypersensitivity response upon a specific allergen challenge, which is possibly inversely linked with the erythrocyte numbers.(VLID)460635

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

Effects of nasal corticosteroids on boosts of systemic allergen-specific IgE production induced by nasal allergen exposure.

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

The Fish in the Turtle: On the Functionality of the Oropharynx in the Common Musk Turtle Sternotherus odoratus (Chelonia, Kinosternidae) Concerning Feeding and Underwater Respiration

In tetrapods, the oropharyngeal cavity and its anatomical structures are mainly, but not exclusively, responsible for the uptake and intraoral transport of food. In this study, we provide structural evidence for a second function of the oropharynx in the North American common musk turtle, Sternotherus odoratus, Kinosternidae: aquatic gas exchange. Using high-speed video, we demonstrate that S. odoratus can grasp food on land by its jaws, but is afterward incapable of lingual based intraoral transport; food is always lost during such an attempt. Scanning electron microscopy and light microscopy reveal that the reason for this is a poorly developed tongue. Although small, the tongue bears a variety of lobe-like papillae, which might be misinterpreted as an adaptation for terrestrial food uptake. Similar papillae also cover most of the oropharynx. They are highly vascularized as shown by light microscopy and may play an important role in aquatic gas exchange. The vascularization of the oropharyngeal papillae in S. odoratus is then compared with that in Emys orbicularis, an aquatic emydid with similar ecology but lacking the ability of underwater respiration. Oropharyngeal papillae responsible for aquatic respiration are also found in soft-shelled turtles (Trionychidae), the putative sister group of the kinosternids. This trait could therefore represent a shared, ancestral character of both groups involving advantages in the aquatic environment they inhabit

Development of Bet v 1-specific antibody responses.

<p>Percentage changes of Bet v 1-specific IgG₁, IgG₂, IgG₄, IgA and IgM antibody levels (y-axes) at the day of the first nasal provocation (0) and thereafter (x-axes). Uninterrupted lines: Patients with steroid spray; dotted lines: Patients with placebo spray; black squares: provocation with rPhl p 5; grey dots: provocation with rBet v 1.</p

Distribution of study subjects.

<p>Of the 48 volunteers who were randomized, 45 completed the trial. Drop-outs are marked in yellow. INCS: intranasal corticosteroid; NPT: nasal provocation test; URTI: upper respiratory tract infection; i.m.: intra-muscular</p

Development of allergen-specific IgE levels.

<p>Relative changes of IgE-levels (y-axes) to Phl p 5, Bet v 1 and Phl p 1 (top to bottom: right labels of each chart) compared to t1 (day 1) are shown for all visits (t2: day 8; t3: day 15; t4: day 29; t5: day 43; t6: day 57, x-axes). Results for the steroid-treated group are shown in blue, the placebo-group in green. Results from participants challenged with Phl p 5 are depicted in the left column, those for the Bet v 1-challenged group on the right side. Outliers that lie between 1.5 and 3 times the interquartile range below the first or above the third quartile are shown as open circles (“o”), those that lie beyond 3 times the interquartile range are depicted by asterisks (“*”).There were no significant differences between the fluticasone and placebo groups at any time point.</p

Development of Phl p 5-specific antibody responses.

<p>Percentage changes of Phl p 5-specific IgG₁, IgG₂, IgG₄, IgA and IgM antibody levels (y-axes) at the day of the first nasal provocation (0) and thereafter (x-axes). Uninterrupted lines: Patients with steroid spray; dotted lines: Patients with placebo spray; black squares: provocation with rPhl p 5; grey dots: provocation with rBet v 1.</p