Allergenicity to worldwide invasive grass Cortaderia selloana as environmental risk to public health.

Allergies to grass pollen affects about 20% of the population worldwide. In the last few decades, the South American grass Cortaderia selloana (CS, Pampas grass) has expanded worldwide in a variety of countries including the USA, Australia and Western Europe. In many of these locations, CS has strikingly spread and has now been classified an invasive species. Many pernicious consequences of CS have been reported for local biodiversity, landscape and structures. However, the effect on human health has not been studied. To investigate this issue, we have chosen a European region on the northern cost of Spain where CS spread is overwhelming, Cantabria. We obtained CS pollen extract and analysed the allergenic reaction of 98 patients that were allergic to pollen of local grasses. We determined the skin reaction and the presence of specific IgE antibodies (sIgE) to CS or to a typical autochthonous grass, Phleum pratense. We also compared the seasonal symptoms with reported grass pollen counts in the area. The results strongly suggest that CS can cause respiratory allergies at a similar extent to the local grasses. Given that CS pollinises later than the local grasses, this would extend the period of grass allergies in the region for about three months every year, as stated by most of the patients. This is the first study reported on the effects of the striking expansion of CS on human health. Considering the strong impact that respiratory allergies have on the population, our results suggest that CS can currently constitute a relevant environmental health issue.

The Relationship between Aeroallergen Sensitization and Chronic Cough in School-Aged Children from General Population.

OBJECTIVE: Determining sensitivity to allergens is an essential step in diagnosing children with allergic diseases. Chronic cough has remained poorly understood with causative triggers. The purpose of our study was to shed light on the relationship between sensitization to aeroallergens and chronic cough. METHODS: This population-based study examined children (aged 7 years to 13 years) between June and July 2016. The 1,259 children, 72 of whom (5.7%) had a chronic cough, and 1,187 of whom (94.3%) did not (controls), completed the questionnaire, but 1,051 children completed skin prick tests (SPTs) with eight aeroallergens. RESULTS: There were positive SPT results to at least 1 allergen in 549 children (52.2%). Sensitization to house dust mite (HDM) was most common (chronic cough = 46.9%; controls = 47.2%), followed by pollen (chronic cough = 21.9%; controls = 16.5%) in both groups, but there was no difference in allergic profile and sensitization to aeroallergen (P > 0.05 for all comparisons). Multivariable analysis with adjustment for confounding indicated that children who were in sensitization to pollen had an increased risk of chronic cough (aOR = 2.387; 95% CI: 1.115 to 5.111; P = 0.025). Multivariable analysis with adjustment for confounding indicated that children who were exposed to current smoking (aOR = 4.442; 95% CI: 1.831 to 10.776; P = 0.001) and mold (aOR = 1.988; 95% CI: 1.168 to 3.383; P = 0.011) were associated with chronic cough. CONCLUSION: Sensitization to pollen should be considered as a potential contributing factor to the development of chronic cough in school-aged children.

Lactic Acid Bacteria Fermented Cordyceps militaris (GRC-SC11) Suppresses IgE Mediated Mast Cell Activation and Type I Hypersensitive Allergic Murine Model.

Cordyceps militaris (C. militaris) has various biomedical applications in traditional oriental medicine for different diseases including inflammatory and immune-dysregulated diseases. It is a reservoir of nutritional components such as cordycepin, polysaccharides, and antioxidants. To improve its bioactivity, we fermented C. militaris with a Pediococcus pentosaceus strain isolated from a salted small octopus (SC11). The current study aimed to evaluate whether P. pentosaceus (SC11) fermentation could enhance the anti-allergic potential of C. militaris cultured on germinated Rhynchosia nulubilis (GRC) against a type I hypersensitive reaction in in vitro and in vivo studies. Total antioxidant capacity and cordycepin content were significantly increased in GRC after SC11 fermentation. GRC-SC11 showed significantly enhanced anti-allergic responses by inhibiting immunoglobulin E (IgE)/antigen-induced degranulation in RBL-2H3 cells, compared to GRC. The results demonstrated the significant inhibition of phosphorylated spleen tyrosine kinase (Syk)/ p38/GRB2-associated binding protein 2 (Gab2)/c-jun in IgE/Ag-triggered RBL-2H3 cells. Furthermore, suppressed mRNA levels of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in IgE/Ag-activated RBL-2H3 cells were observed. GRC-SC11 significantly ameliorated IgE-induced allergic reactions by suppressing the ear swelling, vascular permeability, and inflammatory cell infiltration in passive cutaneous anaphylaxis (PCA) BALB/c mice. In conclusion, GRC fermented with P.pentosaceus exerted enhanced anti-allergic effects, and increased the cordycepin content and antioxidants potential compared to GRC. It can be used as bio-functional food in the prevention and management of type I allergic diseases.

Current possibilities and future perspectives for improving efficacy of allergen-specific sublingual immunotherapy.

Allergen-specific sublingual immunotherapy (SLIT), a safe and efficient route for treating type I hypersensitivity disorders, requires high doses of allergens. SLIT is generally performed without adjuvants and delivery systems. Therefore, allergen formulation with appropriate presentation platforms results in improved allergen availability, targeting the immune cells, inducing regulatory immune responses, and enhancing immunotherapy's efficacy while decreasing the dose of the allergen. In this review, we discuss the adjuvants and delivery systems that have been applied as allergen-presentation platforms for SLIT. These adjuvants include TLRs ligands, 1α, 25-dihydroxy vitamin D3, galectin-9, probiotic and bacterial components that provoke allergen-specific helper type-1 T lymphocytes (TH1), and regulatory T cells (Tregs). Another approach is encapsulation or adsorption of the allergens into a particulate vector system to facilitate allergen capture by tolerogenic dendritic cells. Also, we proposed strategies to increasing the efficacy of SLIT via new immunopotentiators and carrier systems in the future.

Brown Seaweed Food Supplementation: Effects on Allergy and Inflammation and Its Consequences.

Multiple health benefits have been ascribed to brown seaweeds that are used traditionally as dietary component mostly in Asia. This systematic review summarizes information on the impact of brown seaweeds or components on inflammation, and inflammation-related pathologies, such as allergies, diabetes mellitus and obesity. We focus on oral supplementation thus intending the use of brown seaweeds as food additives. Despite the great diversity of experimental systems in which distinct species and compounds were tested for their effects on inflammation and immunity, a remarkably homogeneous picture arises. The predominant effects of consumption of brown seaweeds or compounds can be classified into three categories: (1) inhibition of reactive oxygen species, known to be important drivers of inflammation; (2) regulation, i.e., in most cases inhibition of proinflammatory NF-κB signaling; (3) modulation of adaptive immune responses, in particular by interfering with T-helper cell polarization. Over the last decades, several inflammation-related diseases have increased substantially. These include allergies and autoimmune diseases as well as morbidities associated with lifestyle and aging. In this light, further development of brown seaweeds and seaweed compounds as functional foods and nutriceuticals might contribute to combat these challenges.

The Diagnostic Importance of Recombinant Allergen IgE Testing in Patients with Hymenoptera Venom Allergy: Comparison of Two Methods.

Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting. In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP. We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods. The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HV allergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms. IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts.

TLR2 deficiency promotes IgE and inhibits IgG1 class-switching following ovalbumin sensitization.

BACKGROUND: To explore the roles of Toll-like receptor (TLR)2 in Th2 cytokine production and immunoglobulin (Ig) class switching following ovalbumin (OVA) sensitization. METHODS: TLR2-/- and wild-type C57BL/6 mice were sensitized by intraperitoneal injection with OVA. Lung pathology was assessed by hematoxylin and eosin staining. Abundance of interleukin (IL)4, IL5, IL13, and IL21 transcripts in the lungs was quantified by RT-PCR. OVA-specific IgG1, IgG2a, IgG2b, IgE and IgM were quantified by enzyme-linked immunosorbent assay. Phosphorylated signal transducer and activator of transcription (STAT)3 in lung tissue was detected by immunohistochemistry staining and nuclear factor (NF) κB activation was measured by immunofluorescence staining. STAT3 activation was inhibited using cryptotanshinone (CPT) treatment. Germline transcripts (Iµ-Cµ, Iγ-Cγ, Iα-Cα or Iε-Cε), post-recombination transcripts (Iµ-Cγ, Iµ-Cα or Iµ- Cε) and mature transcripts (VHDJH-Cγ, VHDJH-Cα or VHDJH-Cε) were analyzed from splenic B cells of OVA-sensitized wild-type mice (with or without CPT treatment) and TLR2-/- mice (with or without IL21 treatment). RESULTS: The lungs of TLR2-/- mice showed a lesser degree of inflammation than wild-type mice after OVA sensitization. Following OVA sensitization, levels of IL4, IL13, and IL21, but not IL5, were significantly lower in TLR2-/- compared with wild-type mice. Moreover, OVA-specific IgG1 and IgE titers were markedly lower and higher, respectively, in TLR2-/- mice. TLR2 deficiency inhibited STAT3 activation but not NF-κB p65 activation. CPT treatment reduced IgG1 titers via inhibition of Stat3 phosphorylation. Both TLR2 knockout and CPT treatment reduced the frequencies of Iγ1-Cγ1, Iγ3-Cγ3 and Iα-Cα transcripts, but IL21 treatment compensated for the effects of TLR2 deficiency. CONCLUSION: These results suggest a role of TLR2 in restricting OVA-sensitized lung inflammation via promotion of IgG1 and inhibition of IgE class switching regulated by IL21 and STAT3.

Tectochrysin ameliorates murine allergic airway inflammation by suppressing Th2 response and oxidative stress.

Tectochrysin, a flavonoid compound, can be isolated from propolis, Alpinia oxyphylla Miq, and Lychnophora markgravii. This study evaluated the efficacy of tectochrysin in the treatment of shrimp tropomyosin (ST)-induced mouse asthma. Mice were sensitized with intraperitoneal (i.p.) injection of ST together with aluminum hydroxide as an adjuvant to establish a mouse model of asthma. Mice were i.p.-treated daily with tectochrysin. IgE levels in plasma, Th2 cytokines from both bronchoalveolar lavage (BAL) fluid and splenocytes, and CD200R on basophils in peripheral blood were measured. Histological analyses of lung tissues and accumulation of leukocytes in BAL fluid were performed. Lung eosinophil peroxidase, catalase and glutathione peroxidase activities were examined. ST was found to markedly increase eosinophilic inflammation and Th2 response in mice. Tectochrysin treatment reduced the level of IgE in plasma, the percentage of eosinophils in total white blood cells in peripheral blood, the total number of cells in BAL fluid, and eosinophil peroxidase activity in lung tissues. Tectochrysin attenuated ST-induced infiltration of eosinophils and epithelial mucus secretion in lung tissues and suppressed the overproduction of Th2 cytokines (IL-4 and IL-5) in BAL fluid. Tectochrysin also attenuated Th2 cytokine (IL-4 and IL-5) production from antigen-stimulated murine splenocytes in vitro, decreased the expression of CD200R on basophils in peripheral blood of asthmatic mice and inhibited IL-4 secretion from IgE-sensitized RBL-2H3 cells. In addition, tectochrysin enhanced catalase and glutathione peroxidase activities in lung tissues. Our findings demonstrate that TEC ameliorates allergic airway inflammation by suppressing Th2 response and oxidative stress.

Vitamin D and Allergy Susceptibility during Gestation and Early Life.

Worldwide, the prevalence of allergies in young children, but also vitamin D deficiency during pregnancy and in newborns is rising. Vitamin D modulates the development and activity of the immune system and a low vitamin D status during pregnancy and in early life might be associated with an increased risk to develop an allergy during early childhood. This review studies the effects of vitamin D during gestation and early life, on allergy susceptibility in infants. The bioactive form of vitamin D, 1,25(OH)2D, inhibits maturation and results in immature dendritic cells that cause a decreased differentiation of naive T cells into effector T cells. Nevertheless, the development of regulatory T cells and the production of interleukin-10 was increased. Consequently, a more tolerogenic immune response developed against antigens. Secondly, binding of 1,25(OH)2D to epithelial cells induces the expression of tight junction proteins resulting in enhanced epithelial barrier function. Thirdly, 1,25(OH)2D increased the expression of anti-microbial peptides by epithelial cells that also promoted the defense mechanism against pathogens, by preventing an invasive penetration of pathogens. Immune intervention by vitamin D supplementation can mitigate the disease burden from asthma and allergy. In conclusion, our review indicates that a sufficient vitamin D status during gestation and early life can lower the susceptibility to develop an allergy in infants although there remains a need for more causal evidence.

Identification and Purification of Novel Low-Molecular-Weight Lupine Allergens as Components for Personalized Diagnostics.

Lupine flour is a valuable food due to its favorable nutritional properties. In spite of its allergenic potential, its use is increasing. Three lupine species, Lupinus angustifolius, L. luteus, and L. albus are relevant for human nutrition. The aim of this study is to clarify whether the species differ with regard to their allergen composition and whether anaphylaxis marker allergens could be identified in lupine. Patients with the following characteristics were included: lupine allergy, suspected lupine allergy, lupine sensitization only, and peanut allergy. Lupine sensitization was detected via CAP-FEIA (ImmunoCAP) and skin prick test. Protein, DNA and expressed sequence tag (EST) databases were queried for lupine proteins homologous to already known legume allergens. Different extraction methods applied on seeds from all species were examined by SDS-PAGE and screened by immunoblotting for IgE-binding proteins. The extracts underwent different and successive chromatography methods. Low-molecular-weight components were purified and investigated for IgE-reactivity. Proteomics revealed a molecular diversity of the three species, which was confirmed when investigated for IgE-reactivity. Three new allergens, L. albus profilin, L. angustifolius and L. luteus lipid transfer protein (LTP), were identified. LTP as a potential marker allergen for severity is a valuable additional candidate for molecular allergy diagnostic tests.

Efficacy of sublingual immunotherapy tablets in dust mite and pollen allergy.

The latest evidence on the mechanisms, efficacy, and safety of sublingual immunotherapy (SLIT) was reviewed. Interleukin (IL) 35 and IL-35-producing regulatory T cells were assessed as new biomarkers for SLIT responsiveness. A detailed analysis of clinical studies, including timothy grass pollen, 5-grass pollen, ragweed, and house-dust mite SLIT tablets, was provided, including a comparative analysis of efficacy and safety of SLIT versus subcutaneous immunotherapy.

Allergy to oak pollen in North America.

Background: Oak pollen is an important allergen in North America. The genus Quercus (oak) belongs to the family Fagaceae under the order Fagales. Objective: The objective of this article was to narratively review the oak pollen season, clinical and epidemiologic aspects of allergy to oak pollen, oak taxonomy, and oak allergen cross-reactivity, with a focus on the North American perspective. Methods: A PubMed literature review (no limits) was conducted. Publications related to oak pollen, oak-related allergic rhinitis with or without conjunctivitis, and oak-related allergic asthma were selected for review. Results: Oak species are common throughout the United States and contribute up to 50% to overall atmospheric pollen loads. Mean peak oak pollen counts can reach >2000 grains/m³. The start of the oak pollen season generally corresponds to the seasonal shift from winter to spring based on latitude and elevation, and may begin as early as mid February. The duration of the season can last > 100 days and, in general, is longer at lower latitudes. In the United States, ∼30% of individuals with allergy are sensitized to oak. The oak pollen season correlates with increased allergic rhinitis symptom-relieving medication use and asthma-related emergency department visits or hospitalizations. Oak falls within the birch homologous group. Extensive immunologic cross-reactivity has been demonstrated between oak pollen and birch pollen allergens, and, more specifically, their major allergens Que a 1 and Bet v 1. The cross-reactivity between oak and birch has implications for allergy immunotherapy (AIT) because guidelines suggest selecting one representative allergen within a homologous group for AIT, a principle that would apply to oak. Conclusion: Allergy to oak pollen is common in North America and has a substantial clinical impact. Oak pollen allergens are cross-reactive with birch pollen allergens, which may have implications for AIT.

The anti-allergic potential of tea: a review of its components, mechanisms and risks.

Allergy is an immune-mediated disease with increasing prevalence worldwide. Regular treatment with glucocorticoids and antihistamine drugs for allergy patients is palliative rather than permanent. Daily use of dietary anti-allergic natural products is a superior way to prevent allergy and alleviate the threat. Tea, as a health-promoting beverage, has multiple compounds with immunomodulatory ability. Persuasive evidence has shown the anti-allergic ability of tea against asthma, food allergy, atopic dermatitis and anaphylaxis. Recent advances in potential anti-allergic ability of tea and anti-allergic compounds in tea have been reviewed in this paper. Tea exerts its anti-allergic effect mainly by reducing IgE and histamine levels, decreasing FcεRI expression, regulating the balance of Th1/Th2/Th17/Treg cells and inhibiting related transcription factors. Further research perspectives are also discussed.

The evolution of allergy immunotherapy.

OBJECTIVE: The objective of this review is to trace the evolution of the art and science of allergy immunotherapy (AIT). DATA SOURCES: Original reports relating to the evolution of the concept of respiratory allergy and its specific treatment were identified by following references in journal articles, review articles, and allergy textbooks from the mid-20th century to the present. STUDY SELECTIONS: Studies highlighting substantial milestones in the evolution of the practice of allergy immunotherapy were included. RESULTS: The story of AIT begins with the recognition of hay fever as a distinct entity and subsequent studies that established grass pollen as one of the causes. This knowledge led several investigators, most notable Leonard Noon and John Freeman who worked at St. Mary's Hospital in London, to attempt to induce tolerance giving grass pollen extract by injection to their patients. After the publication of the work of Noon and Freeman in 1911, the practice of AIT spread rapidly and was applied to many other pollen allergens besides grass and for perennial rhinitis and asthma. The early studies were largely anecdotal, but over the past 60 to 70 years, studies of AIT have been conducted with increasingly sophisticated scientific methods. Nowadays, not only is the practice of AIT based on carefully conducted studies, but the underlying immunologic basis of allergy and the response to AIT have also been and still are being firmly established. CONCLUSION: Both the art and the science behind the practice of AIT have been established by a solid base of clinical and immunologic studies.

Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells.

BACKGROUND: Peanut is a potent inducer of proallergenic TH2 responses in susceptible individuals. Antigen-presenting cells (APCs) including dendritic cells and monocytes instruct naive T cells to differentiate into various effector cells, determining immune responses such as allergy and tolerance. OBJECTIVE: We sought to detect peanut protein (PN)-induced changes in gene expression in human myeloid dendritic cells (mDCs) and monocytes, identify signaling receptors that mediate these changes, and assess how PN-induced genes in mDCs impact their ability to promote T-cell differentiation. METHODS: mDCs, monocytes, and naive CD4+ T cells were isolated from blood bank donors and peanut-allergic patients. APCs were incubated with PN and other stimulants, and gene expression was measured using microarray and RT quantitative PCR. To assess T-cell differentiation, mDCs were cocultured with naive TH cells. RESULTS: PN induced a unique gene expression profile in mDCs, including the gene that encodes retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in the retinoic acid (RA)-producing pathway. Stimulation of mDCs with PN also induced a 7-fold increase in the enzymatic activity of RALDH2. Blocking antibodies against Toll-like receptor (TLR)1/TLR2, as well as small interfering RNA targeting TLR1/TLR2, reduced the expression of RALDH2 in PN-stimulated APCs by 70%. Naive TH cells cocultured with PN-stimulated mDCs showed an RA-dependent 4-fold increase in production of IL-5 and expression of integrin α4ß7. CONCLUSIONS: PN induces RALDH2 in human APCs by signaling through the TLR1/TLR2 heterodimer. This leads to production of RA, which acts on TH cells to induce IL-5 and gut-homing integrin. RALDH2 induction by PN in APCs and RA-promoted TH2 differentiation could be an important factor determining allergic responses to peanut.

Root extract of Angelica reflexa B.Y.Lee reduces allergic lung inflammation by regulating Th2 cell activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the roots of Angelica reflexa B.Y.Lee (AR) have been used to treat cough, phlegm, neuralgia, and arthralgia in Northeast Asia. AIM OF THE STUDY: The anti-asthmatic effect of AR root extract (ARE) was determined using a murine airway allergic inflammation model and the primary T cell polarization assay. MATERIALS AND METHODS: To evaluate the anti-asthmatic effect of ARE, inflammatory cell infiltration was determined histologically and inflammatory mediators were measured in bronchoalveolar lavage fluid (BALF). Furthermore, the effects of AREs on Th2 cell differentiation and activation were determined by western blotting and flow cytometry. RESULTS: Asthmatic phenotypes were alleviated by ARE treatment, which reduced mucus production, inflammatory cell infiltration (especially eosinophilia), and type 2 cytokine levels in BALF. ARE administration to mice reduced the number of activated Th2 (CD4+CD25+) cells and level of GATA3 in the lungs. Furthermore, ARE treatment inhibited the differentiation of Th2 cells in primary cell culture systems via interferon regulatory factor 4 (IRF4) signaling. CONCLUSIONS: Our findings indicate that the anti-asthmatic effect of AREs is mediated by the reduction in Th2 cell activation by regulating IRF4.

Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5.

Current study investigates the immunomodulatory effects of T. stocksianum using mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were treated with methanolic extract, n-hexane, and ethyl acetate fractions for consecutive 7 days along with intranasal challenge. The mRNA expression levels of interleukin-4 (IL-4), IL-5, Aquaporin-1 (AQP1) and Aquaporin-5 (AQP5) were evaluated using reverse transcription polymerase chain reaction. The data showed that T. stocksianum significantly reduced airway inflammation as indicated by reduced inflammatory cell infiltration in lungs, and attenuated total and differential leukocyte counts both in blood and BALF. Expression levels of pro-inflammatory IL-4 and IL-5 in lungs were also found significantly reduced. T. stocksianum significantly reduced pulmonary edema as indicated by reduced lung wet/dry ratio and goblet cell hyperplasia. AQP1 and AQP5 expression levels were also found elevated in treatment groups. In conclusion, T. stocksianum possesses anti-asthmatic activity which may be attributed to reduction in IL-4 and IL-5 expression levels, and elevation in AQP1 and AQP5 expression levels.

Null association between serum 25-hydroxyvitamin D levels with allergic rhinitis, allergic sensitization and non-allergic rhinitis: A Mendelian randomization study.

BACKGROUND: Previous observational studies have not found a conclusive association between serum 25-hydroxyvitamin D (25(OH)D) levels and allergic rhinitis (AR) or allergic sensitization (AS). OBJECTIVE: To investigate a causal association between 25(OH)D levels with risk of AR and AS, using a two-sample Mendelian randomization (MR) approach. METHODS: Seven single nucleotide polymorphisms (SNPs), previously shown to be associated with serum 25(OH)D levels, were identified as instrumental variables. The primary outcome was AR, and the secondary outcomes were AS and non-allergic rhinitis (NAR). The genome-wide association (GWA) summary statistics of the outcomes were obtained from two cohort studies (EAGLE Consortium and UK Biobank). An MR analysis with random-effects inverse-variance weighted method was performed as the primary analysis to estimate overall effect size (odds ratio [OR] and 95% confidence interval [CI]). Sensitivity analysis using weighted median method and MR-Egger regression method was conducted. A subgroup analysis based on 25(OH)D synthesis-related SNPs was further applied. RESULTS: Serum 25(OH)D levels were not causally associated with risk of AR (OR: 0.960; 95% CI: 0.779-1.184), AS (OR: 1.059; 95% CI: 0.686 to 1.634) or NAR (OR: 0.937; 95% CI: 0.588-1.491). Subgroup analysis also showed null association between 25(OH)D synthesis-related SNPs and the outcomes. Sensitivity analyses yielded similar results. CONCLUSIONS AND CLINICAL RELEVANCE: This MR study found no evidence supporting a causal association between serum 25(OH)D levels and risk of AR, AS and NAR in European-ancestry population. This argues against the previous postulation that vitamin D supplementation is effective in prevention of allergic diseases.

High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma.

Allergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.

Purification and biochemical characterization of Hel a 6, a cross-reactive pectate lyase allergen from Sunflower (Helianthus annuus L.) pollen.

Sunflower pollen was reported to contain respiratory allergens responsible for occupational allergy and pollinosis. The present study describes the comprehensive characterization of a major sunflower allergen Hel a 6. Natural Hel a 6 was purified from sunflower pollen by anion exchange and gel filtration chromatography. Hel a 6 reacted with IgE-antibodies from 57% of 39 sunflower-sensitized patient sera suggesting it to be a major allergen. The patients were of Indian origin and suffering from pollinosis and allergic rhinitis. Hel a 6 exhibited allergenic activity by stimulating mediator release from basophils. Monomeric Hel a 6 displayed pectate lyase activity. The effect of various physicochemical parameters such as temperature, pH, and calcium ion on the functional activity of Hel a 6 revealed a stable nature of the protein. Hel a 6 was folded, and its melting curve showed reversible denaturation in which it refolded back to its native conformation from a denatured state. Hel a 6 displayed a high degree of sequence conservation with the pectate lyase allergens from related taxonomic families such as Amb a 1 (67%) and Art v 6 (57%). The IgE-cross reactivity was observed between Hel a 6 and its ragweed and mugwort homologs. The cross-reactivity was further substantiated by the mediator release when Hel a 6-sensitized effector cells were cross-stimulated with Art v 6 and Amb a 1. Several putative B cell epitopes were predicted and mapped on these 3 allergens. Two antigenic regions were found to be commonly shared by these 3 allergens, which could be crucial for cross-reactivity. In conclusion, Hel a 6 serves as a candidate molecule for diagnosis and immunotherapy for weed allergy.