Mugwort Allergy Research Articles

Art v 1 IgE epitopes of patients and humanized mice are conformational

Worldwide, pollen of the weed mugwort (Artemisiavulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and thecorresponding HLA have been made. We sought to characterize IgE epitopes of Art v 1-sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients' IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy.

Retrospective analysis of epidemic thunderstorm asthma in children in Yulin, northwest China.

An epidemic of thunderstorm asthma in pediatric patients occurred in Yulin, a northwest city of China, on 11 September 2018. We described the epidemic and retrospectively analyzed the demographic and clinical aspects of the involved children. The caseload data of patients were collected from the hospital information system in Yulin Pediatric Hospital. The detailed document of hospitalized children with thunderstorm asthma was sourced from the medical records. The mean number of daily visits to emergency/outpatient department and the daily admission to hospital were 2.7 and 16 times, respectively, than on the other days of September. A gender prominence of males was observed in both emergency/outpatient and inpatient department. Among the 51 hospitalized children with detailed medical records, 56% of them had never experienced or were diagnosed with asthma and 25% had confirmed diagnosis of asthma. Sixty-seven percent had a history of allergic rhinitis during August and September. Seventy-six percent of the hospitalized children presented as moderate asthma. Ninety-four percent of the pediatric patients had positive IgE against mugwort pollen and 78% were monosensitized to pollen. Thunderstorm asthma can affect children, especially who has allergic rhinitis or asthma without preventive management. Mugwort is also an aeroallergen in thunderstorm asthma attacks. Thunderstorm can induce asthma attacks in children with allergic rhinitis owing to mugwort and aggravate symptoms in children with confirmed diagnosis of asthma. Children with mugwort allergy are susceptible to thunderstorm asthma and a preponderance of boys was observed. Better identification of allergic children to mugwort, giving suitable protective measures during thunderstorm and standard therapy to existing allergic situation could be a benefit for children at risk of thunderstorm asthma.

The significance of the levels of IL-4, IL-31 and TLSP in patients with asthma and/or rhinitis.

To investigate the clinical significance of the levels of IL-4, IL-33 and thymic stromal lymphopoietin (TLSP) in patients with asthma and/or rhinitis, then do the simple verification in animals. Levels of IL-4 IL-31, IL-33 and TLSP were detected by ELISA and real-time PCR in 64 asthma patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases), 64 asthma complicated with allergic rhinitis patients (sIgE[+]: 32 cases, sIgE[-]: 32 cases) and 32 healthy controls. Then we detected the IL-4, IL-31, IL-33 and TLSP in the sensitized mice. Results showed that levels of IL-4, IL-31, IL-33 and TSLP in asthma and rhinitis patients, and those complicated with allergic rhinitis, had significant differences compared with the control group (p < 0.05). It was found that the indicators of mugwort and dust mite allergic patients were significantly higher than that of other allergic patients (p < 0.05). We got the same tendency in in vivo experiments. IL-4, IL-31, IL-33 and TSLP may be involved in the pathogenesis of asthma and rhinitis; dust mite and mugwort allergy could increase them significantly.

P053 Prevalence of food allergen sensitization in patients with mugwort allergy

La alergia a la artemisa se ha asociado con el sindrome de alergia oral con apio, mango, manzana, durazno, melon, pimiento, zanahoria, brocoli, coliflor, col, mostaza, ajo y cebolla.

Concomitant sensitization to ragweed and mugwort pollen: who is who in clinical allergy?

BackgroundIn many areas of Europe, double sensitization to ragweed and mugwort is common, and because of the overlapping flowering periods of the 2 plants, it is not possible to diagnose the primary sensitizing allergen source and hence to determine the proper immunotherapy. ObjectivesTo elucidate whether double-sensitized patients are cosensitized or cross-sensitized and, in the latter case, to define the primary sensitizer. MethodsSerum samples from 34 patients with late summer respiratory allergy underwent skin prick testing with whole ragweed, and mugwort extracts were analyzed for their reactivity to recombinant Art v 1 and Amb a 1 by ImmunoCAP and then to Amb a 1, Art v 6, and Art v 1 isoforms by a proteomic approach. In double reactors, the primary sensitizing sources were detected by inhibition experiments. ResultsSerum samples from patients monosensitized to ragweed contained IgE to epitopes specific of all Amb a 1 isoforms. In contrast, serum samples from double reactors found to be primarily sensitized to mugwort reacted to Art v 1 and Art v 6 and cross-reacted to a few Amb a 1 isoforms. Finally, serum samples from double reactors found to be primarily sensitized to ragweed contained IgE reacting to all Amb a 1 isoforms, part of which cross-reacted to Art v 6. We did not find cosensitized patients. ConclusionThis study found that Art v 6 plays an important role in mugwort allergy and that the cross-reactivity between Art v 6 and Amb a 1 is frequent, bidirectional, and clinically relevant in the area of Milan.

Component-resolved diagnosis of peach allergy and its relationship with prevalent allergenic pollens in China

Component-resolved diagnosis of peach allergy and its relationship with prevalent allergenic pollens in China

Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background

BackgroundMugwort pollen allergens represent the main cause of pollinosis in late summer. The major allergen, Art v 1, contains only one single immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36 also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36 -specific T cell receptors can be activated by HLA-DR4 molecules. To understand the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in HLA/peptide-binding and TCR-recognition, we investigated the molecular background of Art v 125-36 /MHC/TCR interactions in the context of HLA-DR1 compared to -DR4.ResultsThe majority of Art v 125-36 -specific T cell lines and clones from HLA-DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally processed Art v 1–peptides when presented by HLA-DR1 or HLA-DR4 expressing antigen presenting cells. However, at limiting peptide concentrations DR1 was more effective in T cell stimulation. In addition, the minimal epitope for 50% of Art v 125-36 -specific T cells was shorter for DR1 than for DR4. In vitro binding assays of Art v 125-36 mutant peptides to isolated DR1- and DR4-molecules indicated similar binding capacities and use of the same register. In silico simulation of Art v 125-36 binding to HLA-DR1 and -DR4 suggested similar binding of the central part of the peptide to either molecule, but a higher flexibility of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1.ConclusionsThe predominance of HLA-DR1 in the response to Art v 125-36 may be explained by subtle conformation changes of the peptide bound to DR1 compared to DR4. Computer simulation supported our experimental data by demonstrating differences in peptide mobility within the HLA-DR complex that may influence TCR-binding. We suggest that the minor differences observed in vitro may be more relevant in the microenvironment in vivo, so that only presentation by HLA-DR1, but not -DR4 permits successful T cell activation.

A New Allergen from Ragweed (Ambrosia artemisiifolia) with Homology to Art v 1 from Mugwort

Art v 1, the major pollen allergen of the composite plant mugwort (Artemisia vulgaris) has been identified recently as a thionin-like protein with a bulky arabinogalactan-protein moiety. A close relative of mugwort, ragweed (Ambrosia artemisiifolia) is an important allergen source in North America, and, since 1990, ragweed has become a growing health concern in Europe as well. Weed pollen-sensitized patients demonstrated IgE reactivity to a ragweed pollen protein of apparently 29-31 kDa. This reaction could be inhibited by the mugwort allergen Art v 1. The purified ragweed pollen protein consisted of a 57-amino acid-long defensin-like domain with high homology to Art v 1 and a C-terminal proline-rich domain. This part contained hydroxyproline-linked arabinogalactan chains with one galactose and 5 to 20 and more alpha-arabinofuranosyl residues with some beta-arabinoses in terminal positions as revealed by high field NMR. The ragweed protein contained only small amounts of the single hydroxyproline-linked beta-arabinosyl residues, which form an important IgE binding determinant in Art v 1. cDNA clones for this protein were obtained from ragweed flowers. Immunological characterization revealed that the recombinant ragweed protein reacted with >30% of the weed pollen allergic patients. Therefore, this protein from ragweed pollen constitutes a novel important ragweed allergen and has been designated Amb a 4.

Prevalence of IgE-Binding to Art v 1, Art v 4 and Amb a 1 in Mugwort-Allergic Patients

Background: Mugwort (Artemisia vulgaris) represents an important source of weed pollen allergens. The objectives of the present study were (i) to analyze the IgE binding profiles in a group of mugwort-allergic patients, (ii) to identify individual marker allergens crucial for the diagnosis of mugwort allergy and (iii) to identify potential crossreactive allergens present in ragweed (Ambrosia artemisiifolia) pollen extract. Methods: Sera from 100 pediatric mugwort-allergic patients were analyzed for their IgE binding pattern to natural mugwort and ragweed pollen proteins, purified natural and recombinant Art v 1, recombinant Art v 4 and recombinant Amb a 1 using immunoblots and ELISA. Results: 91% of the patients’ sera tested displayed IgE binding to one or more mugwort pollen allergens in ELISA and 88% were positive in immunoblot. Purified natural Art v 1 was recognized by 79%, the recombinant protein by 39% of the patients tested and purified recombinant Art v 4 by 34% of the patients’ sera. 67% of the sera displayed crossreactive IgE to one or more ragweed pollen allergens. Recombinant Amb a 1 was noted in only 14% of the mugwort-allergic sera. Conclusions: Allergen-specific in vitro diagnosis was performed in 100 pediatric mugwort-allergic serum samples. Using two allergens (Art v 1 and Art v 4), 91% of the patients could be identified as mugwort pollen-sensitized patients by IgE in vitro tests. Crossreactivity to ragweed pollen allergens was demonstrated by in vitro experiments, suggesting a new important and potent allergen source expanding across Europe.

Molecular and functional analysis of the antigen receptor of Art v 1–specific helper T lymphocytes

Ninety-five percent of patients with mugwort allergy are sensitized to Art v 1, the sole major allergen in mugwort (Artemisia vulgaris) pollen. Sixty-nine percent of patients recognizing the single immunodominant T-cell epitope Art v 1(25-36) have an HLA-DRB1*01 phenotype. We studied cloning and functional expression of a human alphabeta T-cell receptor (TCR) specific for Art v 1(25-36). TCR chains were RT-PCR amplified from an Art v 1(25-36)-specific T-cell clone, retrovirally transferred, and functionally tested in Jurkat T cells or alternatively in peripheral blood T lymphocytes of nonallergic individuals. The alpha-chain of the TCR is composed of TRAV17 and TRAJ45 segments, and the beta-chain uses TRBV18, TRBD1, and TRBJ2-7. Analyses of 23 other Art v 1-specific T-cell clones did not reveal preferential usage of the TRAV17, TRBV18, or other TCR gene families. Efficient TCR transfer into Jurkat T cells was shown by binding of TCR Vbeta18-specific mAb and DRB1*0101/Art v 1 tetramers. Transgenic Jurkat T cells specifically recognized syngeneic EBV B cells pulsed with Art v 1(25-36) peptide and artificial antigen-presenting cells expressing invariant chain::Art v 1 fusion proteins. Moreover, transfer of the TCR into peripheral blood lymphocytes generated T cells that were Art v 1 reactive. Activation of transgenic T cells by artificial antigen-presenting cells was strictly dependent on costimulation. For the first time, a detailed molecular and functional analysis of a human allergen-specific TCR is presented.

Effect of immunotherapy with ISS-ODN and allergen in animal model of mugwort allergy

Effect of immunotherapy with ISS-ODN and allergen in animal model of mugwort allergy

What is the role of the allergic sensitization in Graves’ disease?

Recent data supported the presence of T helper 2 dominance in the immune processes of Graves' disease and allergic diseases. A common role of regulatory T cells in the antigen- (or allergen-) specific immune responses was also demonstrated. To study whether allergic events may play a role in the initiation or progression of autoimmune Graves' disease. The occurrence of seasonal allergy may explain the fluctuation in the onset of Graves' disease. The presence of specific IgE levels against inhalative allergens was investigated in 327 patients with thyroid disease (Graves' disease, Hashimoto's thyroiditis, euthyroid goitre). Western blot method was used for the measurement of allergen-specific IgE levels with densitometric evaluation. Allergic sensitization was found in 88 cases (58%) for Graves' disease, 51 cases (46%) for Hashimoto's thyroiditis and 31 cases (55%) for euthyroid goitre. According to allergens, significant difference was demonstrated by Penicillium notatum, Dermatophagoides farinae, alder - rye (pollens) between Graves' disease (depending ophthalmopathy) and euthyroid goitre. In the four groups based on allergen seasonality, the month of the onset in Graves' disease was associated with the season of early tree and mugwort allergy (P < 0.019 between Graves' disease and Hashimoto's thyroiditis). The number of cases, in whom the onset of Graves' disease in a given month was similar to the month of allergic season, was 17 cases vs 7 cases with Hashimoto's thyroiditis (P < 0.028). The allergic sensitization was more frequent in Graves' disease, and the allergic seasonality may explain the fluctuation in the onset of Graves' disease.

The performance of a component‐based allergen‐microarray in clinical practice

Currently, the diagnosis of IgE-mediated allergy is based on allergen-specific history and diagnostic procedures using natural allergen extracts for in vivo and in vitro tests. The aim of the study was to comparatively analyse a new component-based allergen-microarray and the 'quasi-standard' ImmunoCAP for their clinical relevance in patients with allergic rhinoconjunctivitis to five aeroallergens [house dust mite (HDM), cat dander, birch, grass and mugwort pollen] in a prospective, double-centre study. We enrolled 120 subjects at the two study centres. Allergic patients were defined as having an allergen-specific history plus a concomitant positive skin-prick test (SPT) to natural allergen extracts and specific serum IgE was measured by both methods. Each allergen was analysed separately. The microarray performed equally well in receiver-operating characteristic curve (ROC) analyses when compared with the CAP in cat (23 allergic vs 97 non-allergic, ROC area under the curve microarray 0.950 vs CAP 0.894, P = 0.211), birch (31/89, 0.908 vs 0.878, P = 0.483) and grass pollen (47/73, 0.923 vs 0.915, P = 0.770). It was slightly less sensitive in HDM-allergic subjects (26 allergic vs 94 non-allergic, ROC area microarray 0.808 vs CAP 0.911, P = 0.053) and displayed a reduced sensitivity in the mugwort pollen-allergic patients (17/103, 0.723 vs 0.879, P = 0.032). Component-based testing and the whole-allergen CAP are equally relevant in the diagnosis of grass-, birch- and cat-allergic patients. Although slightly less sensitive, the microarray is sufficient for the diagnosis of HDM-allergic patients, but needs alternative and/or additional components for detecting mugwort allergy.

Native Art v 1 and recombinant Art v 1 are able to induce humoral and T cell-mediated in vitro and in vivo responses in mugwort allergy

Background: Mugwort pollen is an important allergen source in hay fever and pollen-related food allergy. Little is known about the clinical relevance of the major mugwort allergen Art v 1 and its importance in allergy. Objective: In this study we aimed to investigate the allergenicity of mugwort extract compared with the allergenicity of native (n)Art v 1 and recombinant (r)Art v 1, one major allergen of mugwort, in vivo and in vitro. Methods: Thirty-two patients allergic to mugwort and 10 control subjects were investigated by means of skin prick and nasal provocation testing with different concentrations of mugwort extract, nArt v 1, and rArt v 1. nArt v 1 was purified from aqueous mugwort extract, and rArt v 1 was cloned, expressed in Escherichia coli , and then purified. The in vitro allergenicity was measured by means of ImmunoCAP, ELISA, ELISA-inhibition experiments, and T-cell proliferation assays. Results: nArt v 1 and rArt v 1 were able to elicit positive in vivo and in vitro reactions. The IgE-binding capacity, as determined by means of ELISA, was slightly higher for nArt v 1 than for rArt v 1, and both allergens were able to induce T-cell proliferation in sensitized patients. However, rArt v 1 elicited a reduced response in skin and nasal provocation tests compared with nArt v 1. Compared with mugwort extract, both nArt v 1 and rArt v 1 showed lower sensitivity in patients with mugwort allergy in vivo. Conclusions: Art v 1, either in its native or recombinant form, is able to induce allergic reactions in patients with mugwort allergy. rArt v 1 induced comparable humoral and cell-mediated responses in vitro but showed reduced in vivo allergenicity compared with biochemically purified nArt v 1. (J Allergy Clin Immunol 2003;111:1328-36.)

The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope.

Mugwort (Artemisia vulgaris) pollen allergens represent the main cause of pollinosis in late summer in Europe. At least 95% of sera from mugwort pollen-allergic patients contain IgE against a highly glycosylated 24- to 28-kDa glycoprotein. Recently, this major allergen, termed Art v 1, was characterized, cloned in Escherichia coli, and produced in recombinant form. In the present study we characterized and compared the T cell responses to natural (nArt v 1) and recombinant Art v 1 (rArt v 1). In vitro T cell responses to nArt v 1 and rArt v 1 were studied in PBMC, T cell lines (TCL), and T cell clones (TCC) established from PBMC of mugwort-allergic patients. Stimulation of PBMC or allergen-specific TCL with either nArt v 1 or rArt v 1 resulted in comparable proliferative T cell responses. Eighty-five percent of the TCC reactive with rArt v 1 cross-reacted with the natural protein. The majority of the CD4(+)CD8(-)TCR alphabeta(+) Art v 1-specific TCC, obtained from 10 different donors, belonged to the Th2 phenotype. Epitope mapping of TCL and TCC using overlapping peptides revealed a single immunodominant T cell epitope recognized by 81% of the patients. Inhibition experiments demonstrated that the presentation of this peptide is restricted by HLA-DR molecules. In conclusion, the T cell response to Art v 1 is characterized by one strong immunodominant epitope and evidently differs from the T cell responses to other common pollen allergens known to contain multiple T cell epitopes. Therefore, mugwort allergy may be an ideal candidate for a peptide-based immunotherapy approach.

Hypersensitivity to mugwort (Artemisia vulgaris) in patients with peach allergy is due to a common lipid transfer protein allergen and is often without clinical expression.

The observation of mugwort-specific IgE antibodies in patients with peach allergy suggests that mugwort sensitization might play a role in sensitization to peach. We sought to study the clinical manifestations of mugwort hypersensitivity in patients with peach allergy, identify the common allergens, and evaluate their IgE crossreactivity. Patients with oral allergy syndrome for peach and specific IgE antibodies to mugwort were investigated for respiratory symptoms during the mugwort season. Peach and mugwort allergens were identified by means of SDS-PAGE and IgE immunoblotting. Immunoblotting inhibition experiments were done to study cross-reactivity between peach and mugwort and other pollens. Seventeen patients were studied, 10 with no seasonal respiratory symptoms and 7 with clear late summer respiratory symptoms. In IgE immunoblotting the 10 asymptomatic patients reacted only to a 9-kd allergen of both mugwort and peach, whereas the 7 patients with pollinosis reacted to other allergens. Ten patients with mugwort allergy, no history of allergy to peach, and negative results for peach-specific IgE antibodies were also studied. The mugwort 9-kd protein was identified as a lipid transfer protein (LTP) homologous to peach LTP. Immunoblotting inhibition showed that IgE binding to the peach 9-kd band was totally inhibited by 4 microg of peach LTP but only by 400 microg of mugwort LTP, whereas 4 microg of both mugwort and peach LTP totally inhibited the mugwort immunoblotting. The results were similar with other pollens. Patients sensitized only to the 9-kd LTP of mugwort do not present hay fever symptoms, and this sensitization is a consequence of the peach sensitization.